June 5, 2010 (Chicago, Illinois) — For patients with hepatic metastases from primary melanoma, a new minimally invasive regional therapy significantly improved hepatic progression-free survival. Compared with patients who received conventional treatment, those treated with melphalan (Alkeran, GlaxoSmithKline) using the Delcath Percutaneous Hepatic Perfusion system had a 54% reduction in time to tumor progression or death.
According to the study results presented here at the American Society of Clinical Oncology 2010 Annual Meeting, patients who received the novel therapy achieved a median hepatic progression-free survival of 245 days (95% confidence interval [CI],136 - 267), whereas those who received the current standard of care achieved a median of 49 days (95% CI, 43 - 68; P < .001).
However, Dirk Schadendorf, MD, from University Hospital Essen in Germany, noted that a major problem with the study is that it did not try to demonstrate an overall survival benefit.
"A substantial number of patients crossed over, and the overall survival is very close between the 2 groups," said Dr. Schadendorf, who served as a discussant for the study. "This may be due to crossover."
More Options Needed
Only about 25% of patients with liver cancer are eligible for resection, and current treatments for patients with unresectable tumors are limited, the authors note. The median survival for patients with hepatic metastases from primary melanoma is between 6 and 9 months, and few available treatment strategies have a meaningful impact on outcome.
A large number of melanomas will recur, explained lead author James F. Pingpank, MD, FACS, associate professor of surgery at the University of Pittsburgh School of Medicine in Pennsylvania. "The liver is the sole or dominant site of disease in over 80% of cases."
Systemic chemotherapy or immunotherapy often does not halt disease progression. However, regional therapy allows dose escalation to the cancer-bearing region or organ while minimizing systemic exposure and toxicity, said Dr. Pingpank during his presentation. "The delivery of clinically relevant levels of hyperthermia or biologic agents is possible. Regional therapy also eliminates or reduces systemic toxicity."
In this phase 3 study, the authors examined the effectiveness of delivering high doses of melphalan to the liver by hepatic arterial infusion. This trial was initiated after a phase 1 dose-escalation study was conducted. "We saw that we were able to have good delivery to the liver with minimal delivery to general circulation," said Dr. Pingpank.
Progression-Free Survival Improved
From February 2006 to October 2009, 93 patients with hepatic metastases from malignant melanoma were randomized to receive percutaneous hepatic perfusion with melphalan (n = 44) or the standard of care (n = 49), which includes supportive care, systemic or regional chemotherapy, and any appropriate therapy administered at the discretion of the physician.
The mean age of the cohort was 54.8 years, and the majority of patients had not received previous therapy. The trial started as a single-institution study, transitioned to a multicenter trial, and was ultimately conducted in 10 centers.
The primary end point of the study was hepatic progression-free survival, and crossover to the experimental group was permitted at hepatic progression. Secondary end points included assessment of response rate, duration of response, and overall survival.
The regimen consisted of 4 to 6 percutaneous hepatic perfusions at 28- to 35-day intervals, delivering 3.0 mg/kg melphalan in a 30-minute hepatic-artery infusion using a percutaneously placed catheter with hepatic venous hemofiltration and a retrohepatic double-balloon catheter.
There was an overall response rate of 34.1% (n = 15) for patients receiving experimental therapy, and of 2.0% (n = 1) for those receiving standard care (P < .001). No complete responses were observed. A total of 27 (55%) patients who were randomized to standard care crossed over to percutaneous hepatic perfusion upon hepatic progression.
Other Limitations
Dr. Schadendorf pointed out the study had limitations. There are relevant data missing, he said; it is unclear which patients had metastases only to the liver and which had metastasis to other sites.
"Clinical benefits, aside from local control, are also missing," he said. "Crossover, in my view, is a sign of bias, so we don't know the full benefit to the patient."
The study was funded by Delcath Systems. Dr. Pingpank and coauthor J.S. Zager, MD, from the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida, report serving on the scientific advisory board of Delcath Systems.
American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract LBA8512. Presented June 5, 2010.
Δευτέρα 7 Ιουνίου 2010
ASCO 2010-NEW HOPES FOR MEDULLOBLASTOMA
June 6, 2010, Chicago — Two separate presentations here at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting offer hope in the treatment of medulloblastoma, the most common malignant brain tumor in children.
Some 400 to 500 cases of medulloblastoma are diagnosed in children every year in the United States. Treatment with radiation and chemotherapy "can cure these cases, but the treatments leave a lot of long-term side effects. If we can minimize them, we can allow these children to grow up and go to school and college and enjoy the normal life that we all take for granted," said one of the presenters, Amar Gajjar, MD, cochair of the Department of Oncology at St. Jude Children's Research Hospital in Memphis, Tennessee.
One approach to reducing adverse effects is to use proton radiotherapy instead of conventional radiotherapy. A presentation of data on 59 children followed for a median 2 years showed that there is less toxicity. The reduction in toxicity seen is "very promising," said lead author Torunn Yock, MD, from the Massachusetts General Hospital in Boston, which has 1 of only 7 proton radiotherapy centers in the United States.
So far, she said, the results show no significant effect on several measures of neurocognitive functioning, including full scale IQ, and show a lower rate of ototoxicity and endocrine deficiencies than what has been reported with conventional radiotherapy.
Elaborating in an interview with Medscape Oncology, Dr. Yock said that the best data for photon radiotherapy, using intensity-modulated radiotherapy, showed grade 3/4 ototoxicity in 25% of patients, whereas her team's data for proton radiotherapy found a rate of 16%. Photon radiotherapy, especially in younger children, can result in a decline in IQ of about 2 to 4 points per year (an IQ of 100 is average and an IQ below 80 indicates special needs), but her team found no statistically significant decline after proton radiotherapy. In addition, conventional radiotherapy results in 1 or more endocrine deficiencies in more than 50% of patients, whereas proton radiotherapy was associated with such problems in about 29%.
Endocrine deficiencies can include problems with growth and in puberty, resulting from radiation damage to the pituitary and hypothalamus, she explained.
There is a fundamental difference in the dose distribution of proton radiation and photon radiation, Dr. Yock explained. Conventional radiotherapy has both an entrance and an exit dose, whereas proton radiotherapy enters with a lower dose and dissipates all the energy in the tumor in the "Bragg peak," so that there is no exit dose. "This means that the radiotherapy is not damaging the tissue that lies behind the tumor, so it spares more of the normal tissue from unnecessary radiation," she said.
Control of disease was similar with the 2 different radiotherapy approaches, but from the perspective of adverse effects, the proton approach "wins hands down," Dr. Yock said. She told Medscape Oncology that she would recommend this approach in favor of conventional radiotherapy for all children with medulloblastoma, and said that patients have traveled from various parts of the world to receive this treatment at their center.
Self-Selected Patient Population?
Because proton-beam radiotherapy is not a readily available technology and many of the patients have to travel to receive this treatment, this is a fairly selected patient population, so it might not be entirely typical, said Lisa Diller, MD, from the Dana-Farber Cancer Center in Boston, who was approached for comment. One hint of this is the baseline IQ levels, which were higher than would be expected, she added.
Dr. Yock agreed, and said that the average baseline IQ was 107 in this study, whereas in literature children with brain tumors score in the range of 93 to 97. She also agreed that the fact that many families have to travel to receive this treatment does select the patient population — parents often find out about the therapy over the Internet, and then have to fund their own travel and accommodations for around 8 weeks to receive the full course of treatment.
Another caveat is that the comparison between proton radiotherapy and conventional approaches is based on historic controls, Dr. Diller noted, although she said that, so far, the data look promising. It does look as if the proton approach has fewer adverse effects — as one would expect from first principles with irradiating less of a developing brain — but she cautioned that this is "not proven and more follow-up is needed."
Novel Agent
Another new approach to the treatment of medulloblastoma was highlighted at an ASCO press briefing, even though the data were very preliminary, and came from a pilot trial in 12 patients, of whom only 2 had the specific abnormality that was targeted with a novel therapy.
The drug, GDC-0449 (under development by Genentech), targets the sonic hedgehog pathway, which is activated in about 20% of patients with medulloblastoma.
D
r. Gajjar presented results from a trial of the drug in 12 children with relapsed medulloblastoma who had progressed after c
onventional therapy. Two of these children showed activation of the sonic hedgehog pathway: 1 progressed after 5 months on the new drug, and the other is still taking the drug and has remained progression-free for more than a year.
Dr. Gajjar said this was "promising" because medulloblastomas that have progressed have a "dismal prognosis," and only 5% of children are expected to survive; most die in 12 to 18 months, he said.
The drug was very well tolerated, and "some children benefited tremendously," he said. There are now plans for a phase 2 trial in children (up to 22 years of age) with recurrent medulloblastomas, but only in those who show activation of the sonic hedgehog pathway.
Lynn Schuchter, MD, moderator of the press conference and professor of medicine at the Abramson Cancer Center, University of Pennsylvania, in Philadelphia, explained that this abstract was highlighted even though the data are preliminary because it shows a "proof of principle of targeting this important pathway in cancer." She added that it also appears to be important in other cancers.
There has already been quite a bit of excitement among cancer researchers about this sonic hedgehog pathway and the potential for clinical benefit from drugs that target this pathway, even though the clinical results so far come from very small numbers of patients, as reported previously by Medscape Oncology.
Dr. Yock and coauthors report having served as consultants or advisors to IBA and Procure. Dr. Gajjar has disclosed no relevant financial relationships, but one of his coauthors reports acting in a consultancy or advisory role for Genentech, and stock ownership of Curis. Dr. Schuchter reports receiving research funding from Pfizer.
American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract CRA9501, presented June 5, 2010; abstract CRA9507, presented June 6, 2010.
Some 400 to 500 cases of medulloblastoma are diagnosed in children every year in the United States. Treatment with radiation and chemotherapy "can cure these cases, but the treatments leave a lot of long-term side effects. If we can minimize them, we can allow these children to grow up and go to school and college and enjoy the normal life that we all take for granted," said one of the presenters, Amar Gajjar, MD, cochair of the Department of Oncology at St. Jude Children's Research Hospital in Memphis, Tennessee.
One approach to reducing adverse effects is to use proton radiotherapy instead of conventional radiotherapy. A presentation of data on 59 children followed for a median 2 years showed that there is less toxicity. The reduction in toxicity seen is "very promising," said lead author Torunn Yock, MD, from the Massachusetts General Hospital in Boston, which has 1 of only 7 proton radiotherapy centers in the United States.
So far, she said, the results show no significant effect on several measures of neurocognitive functioning, including full scale IQ, and show a lower rate of ototoxicity and endocrine deficiencies than what has been reported with conventional radiotherapy.
Elaborating in an interview with Medscape Oncology, Dr. Yock said that the best data for photon radiotherapy, using intensity-modulated radiotherapy, showed grade 3/4 ototoxicity in 25% of patients, whereas her team's data for proton radiotherapy found a rate of 16%. Photon radiotherapy, especially in younger children, can result in a decline in IQ of about 2 to 4 points per year (an IQ of 100 is average and an IQ below 80 indicates special needs), but her team found no statistically significant decline after proton radiotherapy. In addition, conventional radiotherapy results in 1 or more endocrine deficiencies in more than 50% of patients, whereas proton radiotherapy was associated with such problems in about 29%.
Endocrine deficiencies can include problems with growth and in puberty, resulting from radiation damage to the pituitary and hypothalamus, she explained.
There is a fundamental difference in the dose distribution of proton radiation and photon radiation, Dr. Yock explained. Conventional radiotherapy has both an entrance and an exit dose, whereas proton radiotherapy enters with a lower dose and dissipates all the energy in the tumor in the "Bragg peak," so that there is no exit dose. "This means that the radiotherapy is not damaging the tissue that lies behind the tumor, so it spares more of the normal tissue from unnecessary radiation," she said.
Control of disease was similar with the 2 different radiotherapy approaches, but from the perspective of adverse effects, the proton approach "wins hands down," Dr. Yock said. She told Medscape Oncology that she would recommend this approach in favor of conventional radiotherapy for all children with medulloblastoma, and said that patients have traveled from various parts of the world to receive this treatment at their center.
Self-Selected Patient Population?
Because proton-beam radiotherapy is not a readily available technology and many of the patients have to travel to receive this treatment, this is a fairly selected patient population, so it might not be entirely typical, said Lisa Diller, MD, from the Dana-Farber Cancer Center in Boston, who was approached for comment. One hint of this is the baseline IQ levels, which were higher than would be expected, she added.
Dr. Yock agreed, and said that the average baseline IQ was 107 in this study, whereas in literature children with brain tumors score in the range of 93 to 97. She also agreed that the fact that many families have to travel to receive this treatment does select the patient population — parents often find out about the therapy over the Internet, and then have to fund their own travel and accommodations for around 8 weeks to receive the full course of treatment.
Another caveat is that the comparison between proton radiotherapy and conventional approaches is based on historic controls, Dr. Diller noted, although she said that, so far, the data look promising. It does look as if the proton approach has fewer adverse effects — as one would expect from first principles with irradiating less of a developing brain — but she cautioned that this is "not proven and more follow-up is needed."
Novel Agent
Another new approach to the treatment of medulloblastoma was highlighted at an ASCO press briefing, even though the data were very preliminary, and came from a pilot trial in 12 patients, of whom only 2 had the specific abnormality that was targeted with a novel therapy.
The drug, GDC-0449 (under development by Genentech), targets the sonic hedgehog pathway, which is activated in about 20% of patients with medulloblastoma.
D
r. Gajjar presented results from a trial of the drug in 12 children with relapsed medulloblastoma who had progressed after c
onventional therapy. Two of these children showed activation of the sonic hedgehog pathway: 1 progressed after 5 months on the new drug, and the other is still taking the drug and has remained progression-free for more than a year.
Dr. Gajjar said this was "promising" because medulloblastomas that have progressed have a "dismal prognosis," and only 5% of children are expected to survive; most die in 12 to 18 months, he said.
The drug was very well tolerated, and "some children benefited tremendously," he said. There are now plans for a phase 2 trial in children (up to 22 years of age) with recurrent medulloblastomas, but only in those who show activation of the sonic hedgehog pathway.
Lynn Schuchter, MD, moderator of the press conference and professor of medicine at the Abramson Cancer Center, University of Pennsylvania, in Philadelphia, explained that this abstract was highlighted even though the data are preliminary because it shows a "proof of principle of targeting this important pathway in cancer." She added that it also appears to be important in other cancers.
There has already been quite a bit of excitement among cancer researchers about this sonic hedgehog pathway and the potential for clinical benefit from drugs that target this pathway, even though the clinical results so far come from very small numbers of patients, as reported previously by Medscape Oncology.
Dr. Yock and coauthors report having served as consultants or advisors to IBA and Procure. Dr. Gajjar has disclosed no relevant financial relationships, but one of his coauthors reports acting in a consultancy or advisory role for Genentech, and stock ownership of Curis. Dr. Schuchter reports receiving research funding from Pfizer.
American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract CRA9501, presented June 5, 2010; abstract CRA9507, presented June 6, 2010.
ASCO 2010-IPILIMUMAB IS BACK
June 6, 2010 (Chicago, Illinois) — An experimental therapy for advanced melanoma has been shown to improve overall survival in patients, and is "on the road" to becoming the "new standard of care," said one of its investigators here at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting.
Patients receiving ipilimumab (Bristol-Myers Squibb) plus a peptide vaccine had a median survival of 10 months, compared with 6.4 months for patients receiving the vaccine alone (P < .001).
Ipilimumab also showed, compared with the peptide vaccine, a near doubling of the rates of survival at 12 months (46% vs 25%) and 24 months (24% vs 14%).
Everyone in the 676-patient study had undergone previous treatment for the disease.
It is the first time that a therapy has been shown to improve survival in a phase 3 randomized controlled trial in this setting, said investigator Steven O'Day, MD, from the University of Southern California Keck School of Medicine in Los Angeles.
Dr. O'Day spoke at a press conference at the meeting.
"This is a really significant finding," said Lynn Schucter, MD, from the Abramson Cancer Center at the University of Pennsylvania in Philadelphia, who moderated the press conference. "When melanoma is advanced, we have very little in the way of effective therapies."
Dr. Schucter expects a big response from patients to this news about ipilimumab.
"Our advanced melanoma patients are all going to be asking to go on this drug," she said. The drug is not approved yet, but is being made available in a compassionate-use clinical trial.
Treatment with ipilimumab, which is administered intravenously, included some severe adverse events, including 14 deaths, half of which were immune related, according to study data presented here and published simultaneously online June 5 in the New England Journal of Medicine.
"This is a powerful drug," said Dr. O'Day, who noted that 10% to 15% of immune-related adverse effects were grade 3 or 4 and required immunosuppressive therapy with steroids.
"Steroids were quite successful in the vast majority of patients," said Dr. O'Day, "and they did not affect efficacy."
Ipilimumab is a targeted T-cell antibody, a new class of drugs, said Dr. O'Day. It is directed against an antigen on the surface of T cells. The antigen, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), acts as a brake on the T cell, explained Dr. O'Day. By blocking the brake, the T cell goes into attack mode and kills cancer cells.
Ipilimumab can also overstimulate the immune system and produce a T-cell attack on normal tissue, usually the skin and colon and less commonly the liver and pituitary gland, Dr. O'Day noted. "These are different side effects than what we are used to," he said.
Ipilimumab is not the first immunotherapy for advanced melanoma.
However, interleukin (IL)-2, which is approved by the US Food and Drug Administration, does not produce any response in most patients and has not been proven to improve survival, said Dr. Schucter.
"Finally melanoma doctors are able to manipulate the immune system in a meaningful way for the treatment of advanced melanoma," said Douglas Blayney, MD, about ipilimumab, to Medscape Oncology. Dr. Blayney is outgoing president of ASCO and professor of internal medicine at the University of Michigan Medical School in Ann Arbor.
This is not the first news of ipilimumab's effectiveness in the treatment of melanoma at ASCO; excitement was generated when data from several phase 2 clinical trials were presented at ASCO 2008, as reported at the time by Medscape Oncology.
Since then, the drug has shown activity in prostate cancer that was described as "dramatic," but the report was based on only 2 patients.
Compassionate-Use Study Is Only in the United States
"Patients are going to have a lot of hope about going on this drug," said Dr. Schucter.
Bristol-Myers Squibb has adequate supplies of the drug available for patients who are eligible for its compassionate-use trial, reported Dr. O'Day.
Bristol-Myers Squibb is marketing ipilimumab and cosponsored the new study, along with Medarex, the company that developed the agent and that was eventually bought by Bristol-Myers Squibb.
The compassionate-use study of ipilimumab is ongoing but is limited to 75 centers in the United States. The phase 3 trial reported on by Dr. O'Day at ASCO was a multicenter international trial.
May Be Combined With Targeted Therapy
Approximately 20% to 30% of advanced melanoma patients will receive a benefit from ipilimumab, said Dr. O'Day.
Dr. Schucter said that the "next step" in improving treatment outcomes in the setting might be found by combining ipilimumab, a targeted T-cell antibody, with the investigational PLX4032 (Plexxicon Inc), which is a molecularly targeted therapy and was first reported on at ASCO in 2009. PLX4032 is an oral agent that targets the oncogenic BRAF gene mutation known as V600E, which occurs in about 40% of malignant melanoma patients, Dr. Schucter explained.
Overall survival data are not yet available for PLX4032, but will likely be published soon in the New England Journal of Medicine.
PLX4032 has "unbelievably dramatic responses in terms of tumor shrinkage," said Dr. Schucter.
Dr. Schucter said that the Melanoma Research Foundation is in the planning stages of a study that combines ipilimumab and PLX4032 in patients with metastatic melanoma.
She also said that there will be other possible combinations as more agents are evaluated, including the investigative agent tremelimumab (Pfizer); like PLX4032, it targets BRAF mutations.
Study Details
The new study involved centers from 13 countries in North America, South America, Europe, Asia, and Africa, and enrolled patients between 2004 and 2008.
Patients with unresectable advanced (stage 3/4) melanoma were randomized to 3 treatment groups in a 1:3:1 ratio: ipilimumab plus placebo (n = 137), ipilimumab plus the gp100 vaccine (n = 403), and the gp100 vaccine plus placebo (n = 136). The gp100 vaccine, an experimental melanoma peptide vaccine also designed to stimulate T cells to attack melanoma cells, was used as a comparison group after previous studies showed that it has modest anticancer activity and is superior to IL-2.
To be eligible, patients had to be HLA-A0201-positive because only those patient types are responsive to the gp100 vaccine. Dr. O'Day said that the study results with ipilimumab apply to all patients with melanoma and are not restricted to HLA-A0201-positive patients.
Ipilimumab, at a dose of 3 mg/kg of body weight, was administered with or without gp100 every 3 weeks for up to 4 treatments (induction).
Dr. O'Day said that no difference was detected in survival between the 2 ipilimumab treatment groups — both were about 10 months.
In addition to providing better survival than the vaccine, ipilimumab provided better disease control; after 6 months, the melanoma did not progress in nearly 30% of those receiving ipilimumab, compared with 11% with the vaccine alone.
Ipilimumab was generally well tolerated, but the study authors noted that the "side effects can be life-threatening and may be treatment limiting."
The most common immune-related adverse event was diarrhea (any grade; 27% to 31% of the 2 ipilimumab groups). The problem resolved in about 2 weeks after the administration of corticosteroids, reported the authors.
Reinduction Works Too
Reinduction with ipilimumab at the time of disease progression can also lead to clinical benefit, report the study authors.
Reinduction was allowed within 28 days of documented progression. A total of 32 patients were reinduced per protocol: 8 with ipilimumab, 23 with combination therapy, and 1 with gp100 (6.1%, 7.3%, and 0.8%, respectively, of the total who received initial therapy with each).
Upon reinduction, a partial or complete response or stable disease was achieved by 65% to 75% of patients in the ipilimumab groups and 0% in the gp100 group, according to the investigators.
Steven O'Day reports playing a consultant or advisory role for and receiving honoraria and research funding from Bristol-Meyers Squibb, and receiving research funding from Medarex. Dr. Blayney reports uncompensated consulting relationships with Allos, Cephalon, and BMS; and receiving research funding from Blue Cross Blue Shield of Michigan and the National Comprehensive Cancer Network.
American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract 4, presented June 6, 2010; abstract 8509, presented June 5, 2010.
Patients receiving ipilimumab (Bristol-Myers Squibb) plus a peptide vaccine had a median survival of 10 months, compared with 6.4 months for patients receiving the vaccine alone (P < .001).
Ipilimumab also showed, compared with the peptide vaccine, a near doubling of the rates of survival at 12 months (46% vs 25%) and 24 months (24% vs 14%).
Everyone in the 676-patient study had undergone previous treatment for the disease.
It is the first time that a therapy has been shown to improve survival in a phase 3 randomized controlled trial in this setting, said investigator Steven O'Day, MD, from the University of Southern California Keck School of Medicine in Los Angeles.
Dr. O'Day spoke at a press conference at the meeting.
"This is a really significant finding," said Lynn Schucter, MD, from the Abramson Cancer Center at the University of Pennsylvania in Philadelphia, who moderated the press conference. "When melanoma is advanced, we have very little in the way of effective therapies."
Dr. Schucter expects a big response from patients to this news about ipilimumab.
"Our advanced melanoma patients are all going to be asking to go on this drug," she said. The drug is not approved yet, but is being made available in a compassionate-use clinical trial.
Treatment with ipilimumab, which is administered intravenously, included some severe adverse events, including 14 deaths, half of which were immune related, according to study data presented here and published simultaneously online June 5 in the New England Journal of Medicine.
"This is a powerful drug," said Dr. O'Day, who noted that 10% to 15% of immune-related adverse effects were grade 3 or 4 and required immunosuppressive therapy with steroids.
"Steroids were quite successful in the vast majority of patients," said Dr. O'Day, "and they did not affect efficacy."
Ipilimumab is a targeted T-cell antibody, a new class of drugs, said Dr. O'Day. It is directed against an antigen on the surface of T cells. The antigen, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), acts as a brake on the T cell, explained Dr. O'Day. By blocking the brake, the T cell goes into attack mode and kills cancer cells.
Ipilimumab can also overstimulate the immune system and produce a T-cell attack on normal tissue, usually the skin and colon and less commonly the liver and pituitary gland, Dr. O'Day noted. "These are different side effects than what we are used to," he said.
Ipilimumab is not the first immunotherapy for advanced melanoma.
However, interleukin (IL)-2, which is approved by the US Food and Drug Administration, does not produce any response in most patients and has not been proven to improve survival, said Dr. Schucter.
"Finally melanoma doctors are able to manipulate the immune system in a meaningful way for the treatment of advanced melanoma," said Douglas Blayney, MD, about ipilimumab, to Medscape Oncology. Dr. Blayney is outgoing president of ASCO and professor of internal medicine at the University of Michigan Medical School in Ann Arbor.
This is not the first news of ipilimumab's effectiveness in the treatment of melanoma at ASCO; excitement was generated when data from several phase 2 clinical trials were presented at ASCO 2008, as reported at the time by Medscape Oncology.
Since then, the drug has shown activity in prostate cancer that was described as "dramatic," but the report was based on only 2 patients.
Compassionate-Use Study Is Only in the United States
"Patients are going to have a lot of hope about going on this drug," said Dr. Schucter.
Bristol-Myers Squibb has adequate supplies of the drug available for patients who are eligible for its compassionate-use trial, reported Dr. O'Day.
Bristol-Myers Squibb is marketing ipilimumab and cosponsored the new study, along with Medarex, the company that developed the agent and that was eventually bought by Bristol-Myers Squibb.
The compassionate-use study of ipilimumab is ongoing but is limited to 75 centers in the United States. The phase 3 trial reported on by Dr. O'Day at ASCO was a multicenter international trial.
May Be Combined With Targeted Therapy
Approximately 20% to 30% of advanced melanoma patients will receive a benefit from ipilimumab, said Dr. O'Day.
Dr. Schucter said that the "next step" in improving treatment outcomes in the setting might be found by combining ipilimumab, a targeted T-cell antibody, with the investigational PLX4032 (Plexxicon Inc), which is a molecularly targeted therapy and was first reported on at ASCO in 2009. PLX4032 is an oral agent that targets the oncogenic BRAF gene mutation known as V600E, which occurs in about 40% of malignant melanoma patients, Dr. Schucter explained.
Overall survival data are not yet available for PLX4032, but will likely be published soon in the New England Journal of Medicine.
PLX4032 has "unbelievably dramatic responses in terms of tumor shrinkage," said Dr. Schucter.
Dr. Schucter said that the Melanoma Research Foundation is in the planning stages of a study that combines ipilimumab and PLX4032 in patients with metastatic melanoma.
She also said that there will be other possible combinations as more agents are evaluated, including the investigative agent tremelimumab (Pfizer); like PLX4032, it targets BRAF mutations.
Study Details
The new study involved centers from 13 countries in North America, South America, Europe, Asia, and Africa, and enrolled patients between 2004 and 2008.
Patients with unresectable advanced (stage 3/4) melanoma were randomized to 3 treatment groups in a 1:3:1 ratio: ipilimumab plus placebo (n = 137), ipilimumab plus the gp100 vaccine (n = 403), and the gp100 vaccine plus placebo (n = 136). The gp100 vaccine, an experimental melanoma peptide vaccine also designed to stimulate T cells to attack melanoma cells, was used as a comparison group after previous studies showed that it has modest anticancer activity and is superior to IL-2.
To be eligible, patients had to be HLA-A0201-positive because only those patient types are responsive to the gp100 vaccine. Dr. O'Day said that the study results with ipilimumab apply to all patients with melanoma and are not restricted to HLA-A0201-positive patients.
Ipilimumab, at a dose of 3 mg/kg of body weight, was administered with or without gp100 every 3 weeks for up to 4 treatments (induction).
Dr. O'Day said that no difference was detected in survival between the 2 ipilimumab treatment groups — both were about 10 months.
In addition to providing better survival than the vaccine, ipilimumab provided better disease control; after 6 months, the melanoma did not progress in nearly 30% of those receiving ipilimumab, compared with 11% with the vaccine alone.
Ipilimumab was generally well tolerated, but the study authors noted that the "side effects can be life-threatening and may be treatment limiting."
The most common immune-related adverse event was diarrhea (any grade; 27% to 31% of the 2 ipilimumab groups). The problem resolved in about 2 weeks after the administration of corticosteroids, reported the authors.
Reinduction Works Too
Reinduction with ipilimumab at the time of disease progression can also lead to clinical benefit, report the study authors.
Reinduction was allowed within 28 days of documented progression. A total of 32 patients were reinduced per protocol: 8 with ipilimumab, 23 with combination therapy, and 1 with gp100 (6.1%, 7.3%, and 0.8%, respectively, of the total who received initial therapy with each).
Upon reinduction, a partial or complete response or stable disease was achieved by 65% to 75% of patients in the ipilimumab groups and 0% in the gp100 group, according to the investigators.
Steven O'Day reports playing a consultant or advisory role for and receiving honoraria and research funding from Bristol-Meyers Squibb, and receiving research funding from Medarex. Dr. Blayney reports uncompensated consulting relationships with Allos, Cephalon, and BMS; and receiving research funding from Blue Cross Blue Shield of Michigan and the National Comprehensive Cancer Network.
American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract 4, presented June 6, 2010; abstract 8509, presented June 5, 2010.
ASCO 2010 NEWS
Investigational Drug May Help Improve Survival In Patients With Advanced Breast Cancer.
The Wall Street Journal (6/7, Dooren, subscription required) reports that eribulin, a chemotherapy drug being developed by Eisai Co. Ltd., may help improve survival in patients with advanced breast cancer, according to a study scheduled to be presented at the American Society of Clinical Oncology's annual meeting.
The Los Angeles Times (6/6, Maugh) "Booster Shots" blog reported that investigators "studied 762 women who had failed at least two courses of chemotherapy for breast cancer, and as many as five." Participants "were randomized so that two-thirds received infusions of the drug and the rest received the best treatment their physician thought appropriate." The researchers found that "the median survival for those receiving eribulin was 13.12 months, compared with a median of 10.65 months for those receiving other treatments."
Bloomberg News (6/7, Pettypiece) reports that the drug "contains a synthetic form of a substance first isolated from a marine sponge in 1992, according to Eisai." Eisai "is also investigating whether its medicine can help patients with prostate and lung cancers." Bloomberg adds, "The Food and Drug Administration will decide whether to approve eribulin by Sept. 30...Eisai said last week."
MedPage Today (6/6, Phend) reported, "Eribulin represents a new class of microtubulin inhibitors, which Twelves described as attacking the scaffolding by which cells divide, but at a different point than the taxanes, vinca alkyloids, and other existing microtubulin inhibitors."
Reuters (6/7, Fox) reported that in a telephone interview, ASCO president Dr. Douglas Blayney said, "This is potentially practice changing." HealthDay (6/6, Gardner) and AFP (6/7) also covered the story.
Ipilimumab Nearly Doubles Number Of Late-Stage Melanoma Patients Surviving One Year.
USA Today (6/7, Szabo) reports that, "in a study of two novel treatments -- a therapeutic vaccine called gp100 and an immune stimulator called ipilimumab -- ipilimumab nearly doubled the number of patients surviving one year, found a study presented Saturday at the American Society of Clinical Oncology" meeting and published online by the New England Journal of Medicine. Approximately "25% of those given the vaccine lived one year, compared with 46% of those on ipilimumab," a drug developed by Bristol-Myers Squibb Co.
In a trial of "676 patients with advanced melanoma who had failed to benefit from two treatments currently available, interleukin-2 or dacarbazine," Bloomberg News (6/5, Pettypiece) reported, "ipilimumab kept about a quarter of patients battling late-stage melanoma alive for two years -- about twice the proportion with current therapies." Those patients who took "ipilimumab alone lived an average of 10.1 months, according to the study, almost four months longer than those given the gp100 vaccine."
The AP (6/7, Marchione) reports that ipilimumab "works by helping the immune system fight tumors. The federal Food and Drug Administration has pledged a quick review, and doctors think the drug could be available by the end of this year."
The Chicago Sun-Times (6/5, Thomas) reported, "Metastatic melanoma has become increasingly common in the United States over the past three decades, and death rates are rising faster than with other cancers." Although "ipilimumab isn't a cure for skin cancer, 'this is a huge event in advanced melanoma, where there just are not a lot of good things to do, and the things we do are pretty toxic,' said Dr. Allen Lichter, chief executive officer of the American Society of Clinical Oncology."
MedPage Today (6/5, Phend) reported that "grade 3 or 4 immune-related adverse events occurred in 10% to 15% of ipilimumab-treated patients, compared with 3.0% on gp100 alone. Some, generally mild, adverse effects persisted up to the two-year follow-up point." Notably, "seven of the 14 deaths in the study were associated with immune-related adverse events."
The Wall Street Journal (6/6, Loftus, subscription required), Medscape (6/5, Mulcahy), Reuters (6/57, Steenhuysen), Dow Jones Newswire (6/5, Loftus, subscription required), HealthDay (6/5, Gardner), and AFP (6/6) also covered the story.
Avastin May Extend Progression-Free Survival In Ovarian Cancer Patients.
The Los Angeles Times (6/7, Maugh) reports that "the cancer drug Avastin [bevacizumab] extends progression-free survival by 39% in ovarian cancer patients." This "study, reported Sunday at a Chicago meeting of the American Society of Clinical Oncology, is also the first to use the drug as first-line therapy for ovarian cancer."
The New York Times (6/7, A15, Pollack) reports that the "trial involved 1,873 women with newly diagnosed Stage 3 or Stage 4 ovarian cancer who had undergone surgery to remove as much cancer as possible." Participants "received either standard chemotherapy and a placebo, standard chemotherapy and Avastin, or standard chemotherapy and Avastin followed by as many as 10 months of Avastin by itself." The researchers found that, "for those who got the extended Avastin treatment, it took a median of 14.1 months for the cancer to start worsening, compared with 10.3 months for those who received only standard chemotherapy and the placebo."
USA Today (6/7, Szabo) reports, however, that "a short course of Avastin and chemotherapy didn't appear to offer any benefit, says study author Robert Burger of the Gynecologic Oncology Group." While previous research has "shown that Avastin can help fight relapsed ovarian cancer, this is the first" study "to show it also combats newly diagnosed disease, Burger says."
The Wall Street Journal (6/7, Dooren, subscription required), Bloomberg News (6/6, Waters), the London Times (6/7, Rose), the UK's Daily Mail (6/7, Macrae), Reuters (6/7, Beasley), and MedPage Today (6/6, Smith) also covered the story.
Data Suggest Two Drugs May Be Better Than Gleevec For Patients With Newly Diagnosed CML.
The Wall Street Journal (6/7, Loftus, subscription required) reports that research presented at the American Society of Clinical Oncology meeting and published online in the New England Journal of Medicine suggests that Bristol-Myers Squibb Co.'s Sprycel (dasatinib) and Novartis's Tasigna (nilotinib) may be better than Novartis AG's Gleevec (imatinib) for patients with newly diagnosed chronic myeloid leukemia.
HealthDay (6/5, Reinberg) reported that in one study, "after a year, 77 percent of the patients receiving Sprycel had a complete cytogenetic response, compared with 66 percent of the patients receiving Gleevec." In the other study, "after one year, more patients -- about 80 percent of those receiving Tasigna -- had a complete cytogenetic response, compared with 65 percent of the patients receiving Gleevec." MedPage Today (6/5, Phend) and the Houston Chronicle (6/7, Ackerman) also covered the story.
Experimental Drug Appears To Shrink Tumors In Lung Cancer Patients With Certain Genetic Variations.
The New York Times (6/6, A16, Pollack) reported that researchers were able to significantly shrink "tumors...in a majority of patients with advanced lung cancer marked by a specific genetic abnormality," according to a study "featured Sunday at the main session of the annual meeting of the American Society of Clinical Oncology."
The Wall Street Journal (6/5, Loftus, subscription required) reported that Pfizer scientists believed crizotinib would inhibit a particular enzyme that is known to feed tumors and have some sort of nil effect on anaplastic lymphoma kinase (ALK), which also appears to promote malignant growth. But, according to a 2007 paper, fusion of a gene and the ALK gene contributed to the development of lung cancer.
In the current study, researchers found that "crizotinib, shrank tumors in 64% of patients with advanced lung cancer and kept 90% of cancers in check," USA Today (6/6, Szabo) reported. Apparently, "crizotinib blocks a genetic abnormality found most often in non-smokers, caused when two normal genes fuse together to form a new, cancer-causing gene, called EML4-ALK."
Responses to "crizotinib have lasted up to 15 months so far, and the drug has been rushed into late-stage testing," but it's "way too soon to declare success," the AP (6/5, Marchione) reported. HealthDay (6/5, Gardner) and Bloomberg News (6/6, Pettypiece) also covered the story.
Erbitux Provides No Benefit Among Patients With Early-Stage Colon Cancer.
The Los Angeles Times (6/6, Maugh) "Booster Shots" blog reported, "For the second time in a year, researchers have found that a drug that has proved useful in treating advanced colon cancer provides no benefit in the early stages of the disease."
Speaking during the American Society of Clinical Oncology meeting, researchers explained that they recruited 1,864 patients whose cancer had spread to close lymph nodes, Dow Jones Newswire (6/6, Dooren, subscription required) reported. All participants also carried a normal KRAS gene. Nearly half of the subjects were treated with FOLFOX, while the remaining patients were treated with Erbitux [cetuximab] and chemotherapy. Some three years later, investigators found that 72% of the latter group survived without disease recurrence, compared with the 75% of those who only received chemotherapy.
Notably, the "finding is the latest of at least three studies that have narrowed the scope of a drug that was the first of its kind for colon cancer when approved in 2004," Bloomberg News (6/6, Randall) reported. HealthDay (6/6, Gardner) also covered the story.
Drug Shows Promise In Treating Drug-Resistant Medulloblastomas.
AFP (6/7) reports that "an experimental drug," currently called GDC-0449, "has shown promise in treating" drug-resistant medulloblastomas, "a small study unveiled at the annual American Society of Clinical Oncology conference showed."
HealthDay (6/5, Gardner) reported that "the drug...interrupts the 'sonic hedgehog' pathway, which has been implicated in a number of other cancers; it is involved in 20 percent of cases of children with medulloblastoma." GDC-0449 "has already been shown to have some effectiveness in adults with medulloblastoma that has recurred, as well as with basal cell carcinoma, a type of skin cancer."
MedPage Today (6/6, Phend) reported that "the 13 children with refractory medulloblastoma included in the proof-of-principle study tolerated the drug...with no grade 4 toxicity or any of the dental or bone growth problems that were considered a risk based on animal studies." Researchers reported that "of the two children confirmed to have activation of the hedgehog pathway in their tumor, one progressed after roughly six months of daily oral therapy and the other remains in the study without progression after 391 days of follow-up."
Reuters (6/6, Beasley) reports that, according to the study's lead investigator, "less than five percent of these children survive if they fail primary treatment."
Medscape (6/6, Chustecka) reported that "there are now plans for a phase 2 trial in children (up to 22 years of age) with recurrent medulloblastomas, but only in those who show activation of the sonic hedgehog pathway."
Delivering One Dose Of Radiation To Breast Tumor's Former Site Effectively Prevents Recurrence.
The Chicago Tribune (6/5, Shelton) reported, "Delivering one dose of radiation to the area where a breast tumor was removed is as effective at preventing recurrence as treating the whole breast with radiation for weeks," according to a study appearing in The Lancet paper and presented during the American Society of Clinical Oncology meeting.
The San Francisco Chronicle (6/5, A1, Allday) reported on its front page, "About 15 percent of the women who got the targeted therapy ended up also getting the extended therapy because of hospital protocols." Investigators eventually noted that "there were six recurrences of cancer in the targeted therapy group and five recurrences in the extended therapy group." In addition, "both groups...reported about the same number of complications from radiation, including infections; breakdown of the skin, or delayed healing in the area that was treated; and pain in the breast or nearby areas."
Yet, "the single dose during surgery avoids potential damage to organs such as the heart, lung, and esophagus, which can occur during radiation to the whole breast," BBC News (6/5) reported. HealthDay (6/5, Dotinga) and MedPage Today (6/5, Smith) also covered the story.
New Findings Highlight Cancer's Complexity.
The Wall Street Journal (6/7, Winslow, Loftus, subscription required) reports on some of the research presented at the American Society of Clinical Oncology meeting. Some of the new findings highlight the complexity of the disease. The Journal quotes George Sledge, MD, newly elected president of ASCO, as saying, "Cancer is like cable television." Sledge adds, "Thirty years ago you had three channels. Now you have 500."
Adding Radiation To Standard Hormone Treatments Prolongs Survival In Locally Advanced Prostate Cancer.
The AP (6/5, Marchione) reported, "Doctors are reporting a key advance in treating men with cancer that has started to spread beyond the prostate: survival is significantly better if radiation is added to standard hormone treatments." Researchers found that "74 percent of men receiving both" radiation and standard hormone treatments "were alive versus 66 percent of the others." In fact, "those on both treatments lived an average of six months longer than those given just hormones."
HealthDay (6/6, Gardner) reported that study author Dr. Padraig Warde said that "radiation treatments should be part of the treatment package for this group of patients," during the annual American Society of Clinical Oncology meeting. AFP (6/6) also covered the story.
Denosumab Trumps Zometa In Delaying Fractures In Men Whose Prostate Cancer Spread To Their Bones.
Bloomberg News (6/6, Waters, Randall) reported that investigators have found that "Amgen Inc.'s bone-strengthening drug denosumab delayed fractures and complications longer than Novartis AG's Zometa [zoledronic acid] in men whose prostate cancer had spread to their bones." In fact, according to data presented during the American Society of Clinical Oncology meeting, "men with the malignancy taking denosumab went an average of 20.7 months before they had their first bone complication, compared with the 17.1 months for Zometa users."
Meanwhile, Reuters (6/6, Beasley) reported, another phase III trial involving 1,960 UK patients with newly diagnosed multiple myeloma revealed that Zometa improved survival and reduced the incidence of bone-related issues. Specifically, patients who took the drug, alongside chemotherapy, experienced a 16% reduction in the mortality risk, compared to those who took an older drug. The Wall Street Journal (6/5, Dooren, subscription required) and Dow Jones Newswire (6/5, subscription required) also covered the story.
Battery-Powered Helmet May Benefit Patients With Brain Tumors.
Bloomberg News (6/5, Randall) reported that a "helmet, powered by a six-pound battery pack," may benefit patients with brain tumors, according to a study presented at the annual meeting of the American Society of Clinical Oncology. Researchers found that the helmet "helped patients with recurrent tumors live 7.8 months, compared with a median 6.1 months for patients given the best available chemotherapies or Roche AG's Avastin." Bloomberg added that "the electric fields resonate at a frequency designed to do no harm to healthy brain tissue."
Abraxane May Help Shrink Tumors In Lung Cancer Patients.
Bloomberg News (6/6, Gibson) reported, "Abraxis BioScience Inc.'s Abraxane helped doctors do a better job of shrinking tumors in lung cancer patients, especially those with a hard-to-treat type, a company-sponsored study found." In fact, "using Abraxane in combination with carboplatin, a standard chemotherapy, shrank the tumors in 33 percent of patients getting the drugs, compared with 25 percent when Bristol-Myers Squibb Co.'s Taxol was added to carboplatin, according to data released...at a Chicago meeting of the American Society of Clinical Oncology." Notably, the company "plans to seek US regulatory clearance for the drug's use in lung cancer," and the current "study is the third and final round of testing required for approval."
Adding Everolimus To Herceptin May Benefit Some Patients With Metastatic Breast Cancer.
MedPage Today (6/6, Susman) reported that "adding the targeted agent everolimus (Afinitor) to therapy for women with metastatic breast cancer resistant to trastuzumab (Herceptin) results in clinical benefit for more than a third of patients," according to a study presented at the annual meeting of the American Society of Clinical Oncology. Altogether, "seven of 47 of these advanced cancer patients achieved an objective partial response to therapy and another nine patients had stable disease for at least 24 weeks."
Patients With Cancer Of The Oropharynx May Do Better If Tumor Is HPV-Positive.
MedPage Today (6/5, Smith) reported that "patients with cancer of the oropharynx did significantly better if their tumor showed markers of human papillomavirus (HPV)," according to a study presented at the annual meeting of the American Society of Clinical Oncology. Investigators found, "in a retrospective analysis of patients in a large chemotherapy trial," that "those with HPV-positive tumors had a five-year survival rate of 79% regardless of the type of treatment." The researchers found that patients "whose tumors were HPV-negative had a five-year survival rate of just 31% -- a difference that was statistically significant."
Selenium May Not Prevent Recurrence Among NSCLC Patients.
Medscape (6/5, Mulcahy) reported, "The vast majority of lung cancer patients do not benefit from selenium, according to the results of a major study presented...at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting."
Researchers examined "more than 1,500 stage 1 (early) non-small cell lung cancer patients who had survived their initial bout with the disease," HealthDay (6/5) reported. After surgery, all "remained cancer-free for a minimum of six months post-treatment. Half the patients were placed on a regimen of 200 micrograms of selenium, while the other half took a placebo."
Dr. "Karp said the good news from the study was that in most cases, the curative therapy was just that -- there were only 216 second primaries (in 190 patients) including 84 new lung cancers in 83 patients," MedPage Today (6/6, Smith) reported. "But, analysis showed that the rate of overall second primary tumors was 3.66 per 100 person years of follow-up among patients in the placebo group, compared with 4.11 among those getting the selenium, Karp reported." Moreover, the "difference can't be explained by low adherence, since median compliance was 95%."
Older NSCLC Patients May Also Benefit From More Aggressive Chemotherapy.
MedPage Today (6/6, Phend) reported, "Older patients benefit from more aggressive chemotherapy in non-small cell lung cancer (NSCLC) similar to their younger counterparts," according to a study of 451 patients. "In a trial conducted specifically among those age 70 to 89, a paclitaxel (Taxol)-carboplatin doublet improved overall survival by nearly four months compared with single-agent cytotoxics." And, "this magnitude of improvement is at least as good as seen in a general population of NSCLC, Elisabeth Quoix, MD, of the University Hospital in Strasbourg, France, said at a press conference...at the American Society of Clinical Oncology meeting."
"ASCO President Dr. Douglas Blaney told CNN (6/5, Falco) this study is going to be practice-changing because it shows 'standard chemo is better than kinder, gentler chemo.'" Similarly, "Dr. Mark Kris, chief of thoracic oncology at Memorial-Sloan Kettering Hospital in New York and ASCO spokesman, told CNN the impact of this trial will be 'huge,'" considering the "average age of diagnosis for this type of lung cancer is 71." He went on to say that "'the message of this paper is really important,' because it encourages oncologists to look beyond their patient's chronological age and if the patient is fit enough, doctors should have the 'confidence to give the best treatment available to older adults with the anticipation of getting the same benefits and side effects.'"
Novel Antibody May Improve Head And Neck Cancer Outcomes.
MedPage Today (6/5, Smith) reported that "a novel antibody improved outcomes for patients with advanced and inoperable squamous cell carcinoma of the head and neck," according to a study presented at the annual meeting of the American Society of Clinical Oncology. Investigators found that, "combined with radiation or chemoradiation, the substance -- a fully humanized monoclonal antibody dubbed nimotuzumab -- significantly outperformed either modality alone in an open-label randomized trial." The researchers also found that "there was little serious toxicity -- such as debilitating skin rash -- attributed to the compound."
Retesting Patients With Metastatic Breast Cancer May Predict Trastuzumab-DM1 Effectiveness.
MedPage Today (6/5, Susman) reported, "Retesting patients with metastatic breast cancer to determine if their tumors overexpress HER2 could predict effectiveness of the experimental treatment trastuzumab-DM1 (T-DM1)," according to "a poster presentation at the annual meeting...of the American Society of Clinical Oncology." In one trial, "40.8% of patients who were found to have HER2-positive testing achieved an objective tumor response, compared with 20% of patients whose HER2 levels were normal." During a "second study, 33.8% of patients with HER2-positive tests responded, compared with 4.8% of the patients with normal HER2 expression."
Peretinoin Fails To Meet Expectations Among Patients With Recurrent Liver Cancer.
MedPage Today (6/6, Susman) reported, "Treatment of recurrent liver cancer with the experimental Vitamin A analog peretinoin failed to meet its primary endpoint in showing a progression-free survival benefit over placebo." In fact, according to data presented at the American Society of Clinical Oncology, "43.7% of patients on peretinoin had maintained progression-free survival after three years of therapy, compared with 29.3% of patients on placebo, but that difference failed to reach statistical significance." The research team from Japan did suggest, however, that "the drug may still have promise in hepatocellular carcinoma."
Bevacizumab Raises No New Safety Concerns Among Patients Undergoing Surgery For Gastric Cancers.
MedPage Today (6/5, Susman) reported, "Preliminary analyses find that the addition of bevacizumab (Avastin) does not appear to cause new safety concerns among patients undergoing surgery for gastric cancers." In fact, nearly "27% of the patients receiving the chemotherapy of epirubicin, cisplatin, and capecitabine (Xeloda) both before and after surgery experienced grade 3 neutropenia, compared with 25% of the patients who received the same chemotherapy regimen plus bevacizumab." Thus, UK researchers also pointed out during the American Society of Clinical Oncology meeting, there "was not a great difference in adverse events between those patients being treated with chemotherapy alone or those who were also receiving bevacizumab."
The Wall Street Journal (6/7, Dooren, subscription required) reports that eribulin, a chemotherapy drug being developed by Eisai Co. Ltd., may help improve survival in patients with advanced breast cancer, according to a study scheduled to be presented at the American Society of Clinical Oncology's annual meeting.
The Los Angeles Times (6/6, Maugh) "Booster Shots" blog reported that investigators "studied 762 women who had failed at least two courses of chemotherapy for breast cancer, and as many as five." Participants "were randomized so that two-thirds received infusions of the drug and the rest received the best treatment their physician thought appropriate." The researchers found that "the median survival for those receiving eribulin was 13.12 months, compared with a median of 10.65 months for those receiving other treatments."
Bloomberg News (6/7, Pettypiece) reports that the drug "contains a synthetic form of a substance first isolated from a marine sponge in 1992, according to Eisai." Eisai "is also investigating whether its medicine can help patients with prostate and lung cancers." Bloomberg adds, "The Food and Drug Administration will decide whether to approve eribulin by Sept. 30...Eisai said last week."
MedPage Today (6/6, Phend) reported, "Eribulin represents a new class of microtubulin inhibitors, which Twelves described as attacking the scaffolding by which cells divide, but at a different point than the taxanes, vinca alkyloids, and other existing microtubulin inhibitors."
Reuters (6/7, Fox) reported that in a telephone interview, ASCO president Dr. Douglas Blayney said, "This is potentially practice changing." HealthDay (6/6, Gardner) and AFP (6/7) also covered the story.
Ipilimumab Nearly Doubles Number Of Late-Stage Melanoma Patients Surviving One Year.
USA Today (6/7, Szabo) reports that, "in a study of two novel treatments -- a therapeutic vaccine called gp100 and an immune stimulator called ipilimumab -- ipilimumab nearly doubled the number of patients surviving one year, found a study presented Saturday at the American Society of Clinical Oncology" meeting and published online by the New England Journal of Medicine. Approximately "25% of those given the vaccine lived one year, compared with 46% of those on ipilimumab," a drug developed by Bristol-Myers Squibb Co.
In a trial of "676 patients with advanced melanoma who had failed to benefit from two treatments currently available, interleukin-2 or dacarbazine," Bloomberg News (6/5, Pettypiece) reported, "ipilimumab kept about a quarter of patients battling late-stage melanoma alive for two years -- about twice the proportion with current therapies." Those patients who took "ipilimumab alone lived an average of 10.1 months, according to the study, almost four months longer than those given the gp100 vaccine."
The AP (6/7, Marchione) reports that ipilimumab "works by helping the immune system fight tumors. The federal Food and Drug Administration has pledged a quick review, and doctors think the drug could be available by the end of this year."
The Chicago Sun-Times (6/5, Thomas) reported, "Metastatic melanoma has become increasingly common in the United States over the past three decades, and death rates are rising faster than with other cancers." Although "ipilimumab isn't a cure for skin cancer, 'this is a huge event in advanced melanoma, where there just are not a lot of good things to do, and the things we do are pretty toxic,' said Dr. Allen Lichter, chief executive officer of the American Society of Clinical Oncology."
MedPage Today (6/5, Phend) reported that "grade 3 or 4 immune-related adverse events occurred in 10% to 15% of ipilimumab-treated patients, compared with 3.0% on gp100 alone. Some, generally mild, adverse effects persisted up to the two-year follow-up point." Notably, "seven of the 14 deaths in the study were associated with immune-related adverse events."
The Wall Street Journal (6/6, Loftus, subscription required), Medscape (6/5, Mulcahy), Reuters (6/57, Steenhuysen), Dow Jones Newswire (6/5, Loftus, subscription required), HealthDay (6/5, Gardner), and AFP (6/6) also covered the story.
Avastin May Extend Progression-Free Survival In Ovarian Cancer Patients.
The Los Angeles Times (6/7, Maugh) reports that "the cancer drug Avastin [bevacizumab] extends progression-free survival by 39% in ovarian cancer patients." This "study, reported Sunday at a Chicago meeting of the American Society of Clinical Oncology, is also the first to use the drug as first-line therapy for ovarian cancer."
The New York Times (6/7, A15, Pollack) reports that the "trial involved 1,873 women with newly diagnosed Stage 3 or Stage 4 ovarian cancer who had undergone surgery to remove as much cancer as possible." Participants "received either standard chemotherapy and a placebo, standard chemotherapy and Avastin, or standard chemotherapy and Avastin followed by as many as 10 months of Avastin by itself." The researchers found that, "for those who got the extended Avastin treatment, it took a median of 14.1 months for the cancer to start worsening, compared with 10.3 months for those who received only standard chemotherapy and the placebo."
USA Today (6/7, Szabo) reports, however, that "a short course of Avastin and chemotherapy didn't appear to offer any benefit, says study author Robert Burger of the Gynecologic Oncology Group." While previous research has "shown that Avastin can help fight relapsed ovarian cancer, this is the first" study "to show it also combats newly diagnosed disease, Burger says."
The Wall Street Journal (6/7, Dooren, subscription required), Bloomberg News (6/6, Waters), the London Times (6/7, Rose), the UK's Daily Mail (6/7, Macrae), Reuters (6/7, Beasley), and MedPage Today (6/6, Smith) also covered the story.
Data Suggest Two Drugs May Be Better Than Gleevec For Patients With Newly Diagnosed CML.
The Wall Street Journal (6/7, Loftus, subscription required) reports that research presented at the American Society of Clinical Oncology meeting and published online in the New England Journal of Medicine suggests that Bristol-Myers Squibb Co.'s Sprycel (dasatinib) and Novartis's Tasigna (nilotinib) may be better than Novartis AG's Gleevec (imatinib) for patients with newly diagnosed chronic myeloid leukemia.
HealthDay (6/5, Reinberg) reported that in one study, "after a year, 77 percent of the patients receiving Sprycel had a complete cytogenetic response, compared with 66 percent of the patients receiving Gleevec." In the other study, "after one year, more patients -- about 80 percent of those receiving Tasigna -- had a complete cytogenetic response, compared with 65 percent of the patients receiving Gleevec." MedPage Today (6/5, Phend) and the Houston Chronicle (6/7, Ackerman) also covered the story.
Experimental Drug Appears To Shrink Tumors In Lung Cancer Patients With Certain Genetic Variations.
The New York Times (6/6, A16, Pollack) reported that researchers were able to significantly shrink "tumors...in a majority of patients with advanced lung cancer marked by a specific genetic abnormality," according to a study "featured Sunday at the main session of the annual meeting of the American Society of Clinical Oncology."
The Wall Street Journal (6/5, Loftus, subscription required) reported that Pfizer scientists believed crizotinib would inhibit a particular enzyme that is known to feed tumors and have some sort of nil effect on anaplastic lymphoma kinase (ALK), which also appears to promote malignant growth. But, according to a 2007 paper, fusion of a gene and the ALK gene contributed to the development of lung cancer.
In the current study, researchers found that "crizotinib, shrank tumors in 64% of patients with advanced lung cancer and kept 90% of cancers in check," USA Today (6/6, Szabo) reported. Apparently, "crizotinib blocks a genetic abnormality found most often in non-smokers, caused when two normal genes fuse together to form a new, cancer-causing gene, called EML4-ALK."
Responses to "crizotinib have lasted up to 15 months so far, and the drug has been rushed into late-stage testing," but it's "way too soon to declare success," the AP (6/5, Marchione) reported. HealthDay (6/5, Gardner) and Bloomberg News (6/6, Pettypiece) also covered the story.
Erbitux Provides No Benefit Among Patients With Early-Stage Colon Cancer.
The Los Angeles Times (6/6, Maugh) "Booster Shots" blog reported, "For the second time in a year, researchers have found that a drug that has proved useful in treating advanced colon cancer provides no benefit in the early stages of the disease."
Speaking during the American Society of Clinical Oncology meeting, researchers explained that they recruited 1,864 patients whose cancer had spread to close lymph nodes, Dow Jones Newswire (6/6, Dooren, subscription required) reported. All participants also carried a normal KRAS gene. Nearly half of the subjects were treated with FOLFOX, while the remaining patients were treated with Erbitux [cetuximab] and chemotherapy. Some three years later, investigators found that 72% of the latter group survived without disease recurrence, compared with the 75% of those who only received chemotherapy.
Notably, the "finding is the latest of at least three studies that have narrowed the scope of a drug that was the first of its kind for colon cancer when approved in 2004," Bloomberg News (6/6, Randall) reported. HealthDay (6/6, Gardner) also covered the story.
Drug Shows Promise In Treating Drug-Resistant Medulloblastomas.
AFP (6/7) reports that "an experimental drug," currently called GDC-0449, "has shown promise in treating" drug-resistant medulloblastomas, "a small study unveiled at the annual American Society of Clinical Oncology conference showed."
HealthDay (6/5, Gardner) reported that "the drug...interrupts the 'sonic hedgehog' pathway, which has been implicated in a number of other cancers; it is involved in 20 percent of cases of children with medulloblastoma." GDC-0449 "has already been shown to have some effectiveness in adults with medulloblastoma that has recurred, as well as with basal cell carcinoma, a type of skin cancer."
MedPage Today (6/6, Phend) reported that "the 13 children with refractory medulloblastoma included in the proof-of-principle study tolerated the drug...with no grade 4 toxicity or any of the dental or bone growth problems that were considered a risk based on animal studies." Researchers reported that "of the two children confirmed to have activation of the hedgehog pathway in their tumor, one progressed after roughly six months of daily oral therapy and the other remains in the study without progression after 391 days of follow-up."
Reuters (6/6, Beasley) reports that, according to the study's lead investigator, "less than five percent of these children survive if they fail primary treatment."
Medscape (6/6, Chustecka) reported that "there are now plans for a phase 2 trial in children (up to 22 years of age) with recurrent medulloblastomas, but only in those who show activation of the sonic hedgehog pathway."
Delivering One Dose Of Radiation To Breast Tumor's Former Site Effectively Prevents Recurrence.
The Chicago Tribune (6/5, Shelton) reported, "Delivering one dose of radiation to the area where a breast tumor was removed is as effective at preventing recurrence as treating the whole breast with radiation for weeks," according to a study appearing in The Lancet paper and presented during the American Society of Clinical Oncology meeting.
The San Francisco Chronicle (6/5, A1, Allday) reported on its front page, "About 15 percent of the women who got the targeted therapy ended up also getting the extended therapy because of hospital protocols." Investigators eventually noted that "there were six recurrences of cancer in the targeted therapy group and five recurrences in the extended therapy group." In addition, "both groups...reported about the same number of complications from radiation, including infections; breakdown of the skin, or delayed healing in the area that was treated; and pain in the breast or nearby areas."
Yet, "the single dose during surgery avoids potential damage to organs such as the heart, lung, and esophagus, which can occur during radiation to the whole breast," BBC News (6/5) reported. HealthDay (6/5, Dotinga) and MedPage Today (6/5, Smith) also covered the story.
New Findings Highlight Cancer's Complexity.
The Wall Street Journal (6/7, Winslow, Loftus, subscription required) reports on some of the research presented at the American Society of Clinical Oncology meeting. Some of the new findings highlight the complexity of the disease. The Journal quotes George Sledge, MD, newly elected president of ASCO, as saying, "Cancer is like cable television." Sledge adds, "Thirty years ago you had three channels. Now you have 500."
Adding Radiation To Standard Hormone Treatments Prolongs Survival In Locally Advanced Prostate Cancer.
The AP (6/5, Marchione) reported, "Doctors are reporting a key advance in treating men with cancer that has started to spread beyond the prostate: survival is significantly better if radiation is added to standard hormone treatments." Researchers found that "74 percent of men receiving both" radiation and standard hormone treatments "were alive versus 66 percent of the others." In fact, "those on both treatments lived an average of six months longer than those given just hormones."
HealthDay (6/6, Gardner) reported that study author Dr. Padraig Warde said that "radiation treatments should be part of the treatment package for this group of patients," during the annual American Society of Clinical Oncology meeting. AFP (6/6) also covered the story.
Denosumab Trumps Zometa In Delaying Fractures In Men Whose Prostate Cancer Spread To Their Bones.
Bloomberg News (6/6, Waters, Randall) reported that investigators have found that "Amgen Inc.'s bone-strengthening drug denosumab delayed fractures and complications longer than Novartis AG's Zometa [zoledronic acid] in men whose prostate cancer had spread to their bones." In fact, according to data presented during the American Society of Clinical Oncology meeting, "men with the malignancy taking denosumab went an average of 20.7 months before they had their first bone complication, compared with the 17.1 months for Zometa users."
Meanwhile, Reuters (6/6, Beasley) reported, another phase III trial involving 1,960 UK patients with newly diagnosed multiple myeloma revealed that Zometa improved survival and reduced the incidence of bone-related issues. Specifically, patients who took the drug, alongside chemotherapy, experienced a 16% reduction in the mortality risk, compared to those who took an older drug. The Wall Street Journal (6/5, Dooren, subscription required) and Dow Jones Newswire (6/5, subscription required) also covered the story.
Battery-Powered Helmet May Benefit Patients With Brain Tumors.
Bloomberg News (6/5, Randall) reported that a "helmet, powered by a six-pound battery pack," may benefit patients with brain tumors, according to a study presented at the annual meeting of the American Society of Clinical Oncology. Researchers found that the helmet "helped patients with recurrent tumors live 7.8 months, compared with a median 6.1 months for patients given the best available chemotherapies or Roche AG's Avastin." Bloomberg added that "the electric fields resonate at a frequency designed to do no harm to healthy brain tissue."
Abraxane May Help Shrink Tumors In Lung Cancer Patients.
Bloomberg News (6/6, Gibson) reported, "Abraxis BioScience Inc.'s Abraxane helped doctors do a better job of shrinking tumors in lung cancer patients, especially those with a hard-to-treat type, a company-sponsored study found." In fact, "using Abraxane in combination with carboplatin, a standard chemotherapy, shrank the tumors in 33 percent of patients getting the drugs, compared with 25 percent when Bristol-Myers Squibb Co.'s Taxol was added to carboplatin, according to data released...at a Chicago meeting of the American Society of Clinical Oncology." Notably, the company "plans to seek US regulatory clearance for the drug's use in lung cancer," and the current "study is the third and final round of testing required for approval."
Adding Everolimus To Herceptin May Benefit Some Patients With Metastatic Breast Cancer.
MedPage Today (6/6, Susman) reported that "adding the targeted agent everolimus (Afinitor) to therapy for women with metastatic breast cancer resistant to trastuzumab (Herceptin) results in clinical benefit for more than a third of patients," according to a study presented at the annual meeting of the American Society of Clinical Oncology. Altogether, "seven of 47 of these advanced cancer patients achieved an objective partial response to therapy and another nine patients had stable disease for at least 24 weeks."
Patients With Cancer Of The Oropharynx May Do Better If Tumor Is HPV-Positive.
MedPage Today (6/5, Smith) reported that "patients with cancer of the oropharynx did significantly better if their tumor showed markers of human papillomavirus (HPV)," according to a study presented at the annual meeting of the American Society of Clinical Oncology. Investigators found, "in a retrospective analysis of patients in a large chemotherapy trial," that "those with HPV-positive tumors had a five-year survival rate of 79% regardless of the type of treatment." The researchers found that patients "whose tumors were HPV-negative had a five-year survival rate of just 31% -- a difference that was statistically significant."
Selenium May Not Prevent Recurrence Among NSCLC Patients.
Medscape (6/5, Mulcahy) reported, "The vast majority of lung cancer patients do not benefit from selenium, according to the results of a major study presented...at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting."
Researchers examined "more than 1,500 stage 1 (early) non-small cell lung cancer patients who had survived their initial bout with the disease," HealthDay (6/5) reported. After surgery, all "remained cancer-free for a minimum of six months post-treatment. Half the patients were placed on a regimen of 200 micrograms of selenium, while the other half took a placebo."
Dr. "Karp said the good news from the study was that in most cases, the curative therapy was just that -- there were only 216 second primaries (in 190 patients) including 84 new lung cancers in 83 patients," MedPage Today (6/6, Smith) reported. "But, analysis showed that the rate of overall second primary tumors was 3.66 per 100 person years of follow-up among patients in the placebo group, compared with 4.11 among those getting the selenium, Karp reported." Moreover, the "difference can't be explained by low adherence, since median compliance was 95%."
Older NSCLC Patients May Also Benefit From More Aggressive Chemotherapy.
MedPage Today (6/6, Phend) reported, "Older patients benefit from more aggressive chemotherapy in non-small cell lung cancer (NSCLC) similar to their younger counterparts," according to a study of 451 patients. "In a trial conducted specifically among those age 70 to 89, a paclitaxel (Taxol)-carboplatin doublet improved overall survival by nearly four months compared with single-agent cytotoxics." And, "this magnitude of improvement is at least as good as seen in a general population of NSCLC, Elisabeth Quoix, MD, of the University Hospital in Strasbourg, France, said at a press conference...at the American Society of Clinical Oncology meeting."
"ASCO President Dr. Douglas Blaney told CNN (6/5, Falco) this study is going to be practice-changing because it shows 'standard chemo is better than kinder, gentler chemo.'" Similarly, "Dr. Mark Kris, chief of thoracic oncology at Memorial-Sloan Kettering Hospital in New York and ASCO spokesman, told CNN the impact of this trial will be 'huge,'" considering the "average age of diagnosis for this type of lung cancer is 71." He went on to say that "'the message of this paper is really important,' because it encourages oncologists to look beyond their patient's chronological age and if the patient is fit enough, doctors should have the 'confidence to give the best treatment available to older adults with the anticipation of getting the same benefits and side effects.'"
Novel Antibody May Improve Head And Neck Cancer Outcomes.
MedPage Today (6/5, Smith) reported that "a novel antibody improved outcomes for patients with advanced and inoperable squamous cell carcinoma of the head and neck," according to a study presented at the annual meeting of the American Society of Clinical Oncology. Investigators found that, "combined with radiation or chemoradiation, the substance -- a fully humanized monoclonal antibody dubbed nimotuzumab -- significantly outperformed either modality alone in an open-label randomized trial." The researchers also found that "there was little serious toxicity -- such as debilitating skin rash -- attributed to the compound."
Retesting Patients With Metastatic Breast Cancer May Predict Trastuzumab-DM1 Effectiveness.
MedPage Today (6/5, Susman) reported, "Retesting patients with metastatic breast cancer to determine if their tumors overexpress HER2 could predict effectiveness of the experimental treatment trastuzumab-DM1 (T-DM1)," according to "a poster presentation at the annual meeting...of the American Society of Clinical Oncology." In one trial, "40.8% of patients who were found to have HER2-positive testing achieved an objective tumor response, compared with 20% of patients whose HER2 levels were normal." During a "second study, 33.8% of patients with HER2-positive tests responded, compared with 4.8% of the patients with normal HER2 expression."
Peretinoin Fails To Meet Expectations Among Patients With Recurrent Liver Cancer.
MedPage Today (6/6, Susman) reported, "Treatment of recurrent liver cancer with the experimental Vitamin A analog peretinoin failed to meet its primary endpoint in showing a progression-free survival benefit over placebo." In fact, according to data presented at the American Society of Clinical Oncology, "43.7% of patients on peretinoin had maintained progression-free survival after three years of therapy, compared with 29.3% of patients on placebo, but that difference failed to reach statistical significance." The research team from Japan did suggest, however, that "the drug may still have promise in hepatocellular carcinoma."
Bevacizumab Raises No New Safety Concerns Among Patients Undergoing Surgery For Gastric Cancers.
MedPage Today (6/5, Susman) reported, "Preliminary analyses find that the addition of bevacizumab (Avastin) does not appear to cause new safety concerns among patients undergoing surgery for gastric cancers." In fact, nearly "27% of the patients receiving the chemotherapy of epirubicin, cisplatin, and capecitabine (Xeloda) both before and after surgery experienced grade 3 neutropenia, compared with 25% of the patients who received the same chemotherapy regimen plus bevacizumab." Thus, UK researchers also pointed out during the American Society of Clinical Oncology meeting, there "was not a great difference in adverse events between those patients being treated with chemotherapy alone or those who were also receiving bevacizumab."
A RARE RENAL PEDIATRIC TUMOR
Renal cell carcinoma with Xp11.2 translocation in a 7-year-old boy.
Jayasinghe C, Siegler N, Leuschner I, Fleischhack G, Born M, Müller AM.
Department of Paidopathology, Institute of Pathology, Medical Center, University of Bonn, Germany.
Abstract
BACKGROUND: More than 90% of pediatric renal tumors are nephroblastomas while renal cell carcinomas (RCC) are rare in children (< 5%). PATIENT: According to the clinical diagnoses of a nephroblastoma stage IV a 7-year-old boy with a kidney tumor and peripheral pulmonary lesion was preoperatively treated for 8 weeks with Vincristine, Actinomycin D and Adriamycin. The resected kidney displayed a RCC with Xp11.2 translocation. There was no tumor regression and the pulmonary lesion was no longer detectable. Hence chemotherapy was put to a halt. CONCLUSION: Fine needle aspiration biopsy (FNA) would have allowed to adjust the tumor subtype. Prognosis of pediatric RCC with translocation seems more favourable than without translocation though definitive evidence will only be possible by documentation in a clinical diagnose-related register.
Jayasinghe C, Siegler N, Leuschner I, Fleischhack G, Born M, Müller AM.
Department of Paidopathology, Institute of Pathology, Medical Center, University of Bonn, Germany.
Abstract
BACKGROUND: More than 90% of pediatric renal tumors are nephroblastomas while renal cell carcinomas (RCC) are rare in children (< 5%). PATIENT: According to the clinical diagnoses of a nephroblastoma stage IV a 7-year-old boy with a kidney tumor and peripheral pulmonary lesion was preoperatively treated for 8 weeks with Vincristine, Actinomycin D and Adriamycin. The resected kidney displayed a RCC with Xp11.2 translocation. There was no tumor regression and the pulmonary lesion was no longer detectable. Hence chemotherapy was put to a halt. CONCLUSION: Fine needle aspiration biopsy (FNA) would have allowed to adjust the tumor subtype. Prognosis of pediatric RCC with translocation seems more favourable than without translocation though definitive evidence will only be possible by documentation in a clinical diagnose-related register.
Σάββατο 5 Ιουνίου 2010
WHAT'S HOT AT ASCO
June 3, 2010 — An exclusive interview with the outgoing president of the American Society of Clinical Oncology (ASCO) provides a glimpse of some of the exciting research due to be presented at this year's annual meeting.
Advancing quality through innovation is the theme for this year's meeting; quality of cancer care has been a focus throughout the past year, when Douglas Blayney, MD, professor of internal medicine at the University of Michigan Medical School in Ann Arbor, served as president of ASCO.
"Our whole field is moving toward personalized medicine — which was the theme of last year's ASCO meeting," Dr. Blayney said in an interview with Medscape Oncology.
"The quality aspect is trying to make sure that the right medicine gets to the right patient at the right time," he said. "There is a need for continual innovation and a continuation of personalization of medicine."
Several new studies looking into personalization of medicine will be reported during the meeting, he said.
One study looking into the possibility of personalizing medicine in lung cancer will be unveiled at the plenary session on Sunday, when results will be reported for a novel compound, an oral ALK inhibitor (PF-02341066), in ALK-positive patients with nonsmall-cell lung cancer (abstract 3).
Other research that might lead to personalized medicine is on the HER2-specific agent lapatinib (Tykerb) in the treatment of head and heck cancer (abstract 5505). HER2 was first shown to be important in breast cancer, and at the 2009 ASCO meeting it was shown to be important in gastric cancer in a trial with trastuzumab (Herceptin), as reported by Medscape Oncology at the time.
Phase 3 Trials at Plenary Session
The plenary session will also feature new data from 2 phase 3 clinical trials, one with bevacizumab (Avastin) in ovarian cancer (abstract LBA1), and the other with the novel immunomodulatory compound ipilimumab in metastatic melanoma (abstract 4).
There was excitement about the potential for ipilimumab in the treatment of melanoma when data from several phase 2 clinical trials were presented at ASCO 2008, as reported at the time by Medscape Oncology. Since then, this drug has shown activity in prostate cancer that has been described as "dramatic," but the report was based on only 2 patients.
Another phase 3 clinical trial features a new device for use in the treatment of liver cancer. The device offers percutaneous hepatic perfusion, which isolates the liver from the circulatory system. "There have been a number of devices that have been tried in this cancer," said Dr. Blayney. "Primary hepatic cancer is one of the most common cancers worldwide, and we don't do very well in treating it."
Other clinical data of note feature new chemotherapy agents, including new data on eribulin in metastatic breast cancer (abstract CRA1004^) and updated data on cabazitaxel in prostate cancer (abstract 4058^).
Maintenance Therapy in Hematology
In the hematology field, there are 2 large trials showing benefits from maintenance therapy with rituximab in follicular lymphoma (abstract 8004) and with lenalinomide in multiple myeloma (abstract 8018). Both of these studies were highlighted in an ASCO presscast last week, and the results have already been reported by Medscape Oncology: rituximab and lenalinomide both showed a halving of the risk for relapse when used for maintenance.
Maintenance therapy for myeloma is already common clinical practice, said Dr. Blayney, but there remain questions about which agent to use. One advantage of lenalinomide is that it is taken orally, whereas one of the alternative therapies, bortezomib, needs to be administered intravenously.
With follicular lymphoma, the need for maintenance therapy is less well established; relapses are not as devastating as they are in multiple myeloma. There are 2 schools of thought, Dr. Blayney explained: some clinicians favor maintenance therapy with rituximab to prevent relapses, and others do not use maintenance but treat the relapses as and when they occur.
Other studies that will be presented at the meeting were highlighted in the presscast:
* a study of children cancer survivors that found a genetic susceptibility to the cardiotoxic effects of anthracyclines, even when given at low doses (abstract 9512)
* a study that found little benefit from radiotherapy in elderly patients with early-stage breast cancer treated with lumpectomy and tamoxifen (abstract 507)
* a study showing benefits from yoga on sleep and fatigue in cancer (mostly breast cancer) survivors (abstract 9013)
* a study on screening for ovarian cancer with the CA-125 blood test (abstract 5003).
Quality Certification for Oncology Practices
Coming back to quality of cancer care, Dr. Blayney said that he is particularly proud of the progress made during his presidency in ASCO's Quality Oncology Practice Initiatives (QOPI).
This is a certification that is available to oncology practices that hasn't been available before, Dr. Blayney explained. Previously, certification was available for hospitals and for individual doctors; now it is available for oncology practices. There are training procedures for all staff supporting the oncologist.
Seeing the QOPI through was one of the highlights of his term, Dr. Blayney said. "All of us want to do the right thing for our patients," he said, "and this program offers a way of formalizing that."
As his ASCO presidency draws to a close with a crescendo of activity at the annual meeting, Dr. Blayney said he is looking forward to a quieter time in the year ahead. "My wife will be glad to see some of me," he laughed.
Dr. Blayney reports uncompensated consulting relationships with Allos, Cephalon, and BMS. He also reports receiving research funding from Blue Cross Blue Shield of Michigan and the National Comprehensive Cancer Network.
Advancing quality through innovation is the theme for this year's meeting; quality of cancer care has been a focus throughout the past year, when Douglas Blayney, MD, professor of internal medicine at the University of Michigan Medical School in Ann Arbor, served as president of ASCO.
"Our whole field is moving toward personalized medicine — which was the theme of last year's ASCO meeting," Dr. Blayney said in an interview with Medscape Oncology.
"The quality aspect is trying to make sure that the right medicine gets to the right patient at the right time," he said. "There is a need for continual innovation and a continuation of personalization of medicine."
Several new studies looking into personalization of medicine will be reported during the meeting, he said.
One study looking into the possibility of personalizing medicine in lung cancer will be unveiled at the plenary session on Sunday, when results will be reported for a novel compound, an oral ALK inhibitor (PF-02341066), in ALK-positive patients with nonsmall-cell lung cancer (abstract 3).
Other research that might lead to personalized medicine is on the HER2-specific agent lapatinib (Tykerb) in the treatment of head and heck cancer (abstract 5505). HER2 was first shown to be important in breast cancer, and at the 2009 ASCO meeting it was shown to be important in gastric cancer in a trial with trastuzumab (Herceptin), as reported by Medscape Oncology at the time.
Phase 3 Trials at Plenary Session
The plenary session will also feature new data from 2 phase 3 clinical trials, one with bevacizumab (Avastin) in ovarian cancer (abstract LBA1), and the other with the novel immunomodulatory compound ipilimumab in metastatic melanoma (abstract 4).
There was excitement about the potential for ipilimumab in the treatment of melanoma when data from several phase 2 clinical trials were presented at ASCO 2008, as reported at the time by Medscape Oncology. Since then, this drug has shown activity in prostate cancer that has been described as "dramatic," but the report was based on only 2 patients.
Another phase 3 clinical trial features a new device for use in the treatment of liver cancer. The device offers percutaneous hepatic perfusion, which isolates the liver from the circulatory system. "There have been a number of devices that have been tried in this cancer," said Dr. Blayney. "Primary hepatic cancer is one of the most common cancers worldwide, and we don't do very well in treating it."
Other clinical data of note feature new chemotherapy agents, including new data on eribulin in metastatic breast cancer (abstract CRA1004^) and updated data on cabazitaxel in prostate cancer (abstract 4058^).
Maintenance Therapy in Hematology
In the hematology field, there are 2 large trials showing benefits from maintenance therapy with rituximab in follicular lymphoma (abstract 8004) and with lenalinomide in multiple myeloma (abstract 8018). Both of these studies were highlighted in an ASCO presscast last week, and the results have already been reported by Medscape Oncology: rituximab and lenalinomide both showed a halving of the risk for relapse when used for maintenance.
Maintenance therapy for myeloma is already common clinical practice, said Dr. Blayney, but there remain questions about which agent to use. One advantage of lenalinomide is that it is taken orally, whereas one of the alternative therapies, bortezomib, needs to be administered intravenously.
With follicular lymphoma, the need for maintenance therapy is less well established; relapses are not as devastating as they are in multiple myeloma. There are 2 schools of thought, Dr. Blayney explained: some clinicians favor maintenance therapy with rituximab to prevent relapses, and others do not use maintenance but treat the relapses as and when they occur.
Other studies that will be presented at the meeting were highlighted in the presscast:
* a study of children cancer survivors that found a genetic susceptibility to the cardiotoxic effects of anthracyclines, even when given at low doses (abstract 9512)
* a study that found little benefit from radiotherapy in elderly patients with early-stage breast cancer treated with lumpectomy and tamoxifen (abstract 507)
* a study showing benefits from yoga on sleep and fatigue in cancer (mostly breast cancer) survivors (abstract 9013)
* a study on screening for ovarian cancer with the CA-125 blood test (abstract 5003).
Quality Certification for Oncology Practices
Coming back to quality of cancer care, Dr. Blayney said that he is particularly proud of the progress made during his presidency in ASCO's Quality Oncology Practice Initiatives (QOPI).
This is a certification that is available to oncology practices that hasn't been available before, Dr. Blayney explained. Previously, certification was available for hospitals and for individual doctors; now it is available for oncology practices. There are training procedures for all staff supporting the oncologist.
Seeing the QOPI through was one of the highlights of his term, Dr. Blayney said. "All of us want to do the right thing for our patients," he said, "and this program offers a way of formalizing that."
As his ASCO presidency draws to a close with a crescendo of activity at the annual meeting, Dr. Blayney said he is looking forward to a quieter time in the year ahead. "My wife will be glad to see some of me," he laughed.
Dr. Blayney reports uncompensated consulting relationships with Allos, Cephalon, and BMS. He also reports receiving research funding from Blue Cross Blue Shield of Michigan and the National Comprehensive Cancer Network.
A SELECTIVE ANGIOPOIETIN INHIBITOR
Clin Cancer Res. 2010 May 25. [Epub ahead of print]
Phase 1 Study of AMG 386, a Selective Angiopoietin 1/2-Neutralizing Peptibody, in Combination with Chemotherapy in Adults with Advanced Solid Tumors.
Mita AC, Takimoto CH, Mita M, Tolcher A, Sankhala K, Sarantopoulos J, Valdivieso M, Wood L, Rasmussen E, Sun YN, Zhong ZD, Bass MB, Le N, Lorusso P.
Authors' Affiliations: Institute for Drug Development, San Antonio, Texas; Karmanos Cancer Institute, Detroit, Michigan; and Amgen, Inc., Thousand Oaks, California.
Abstract
PURPOSE: To evaluate the safety, pharmacokinetics, and antitumor activity of AMG 386, an investigational selective angiopoietin 1/2-neutralizing peptibody, in combination with FOLFOX-4 (F), carboplatin/paclitaxel (C/P), or docetaxel (D), in adult patients with advanced solid tumors. EXPERIMENTAL DESIGN: Three cohorts of patients (F, n = 6; C/P, n = 8; D, n = 12) received one full cycle of chemotherapy alone during the pretreatment phase, followed by administration of AMG 386 10 mg/kg i.v. weekly in combination with chemotherapy until disease progression or intolerance. Safety and tolerability, tumor response, pharmacokinetic profiles, and biomarkers were assessed. RESULTS: Twenty-six patients were enrolled; 22 received treatment with AMG 386. No dose-limiting toxicities or grade 3 or 4 adverse events related to AMG 386 were reported. The most common adverse events were diarrhea and hypomagnesemia (n = 3 each). One patient developed grade 2 hypertension and one had grade 1 subconjunctival eye hemorrhage. No neutralizing antibodies to AMG 386 were detected. There were no pharmacokinetic interactions between AMG 386 and F, C/P, or D. One patient receiving AMG 386 plus C/P for bladder cancer refractory to gemcitabine/cisplatin had a complete response at week 8. The remaining best tumor responses were partial response (n = 3, one from each cohort), stable disease >/=8 weeks (n = 13), and progressive disease (n = 1). CONCLUSIONS: Weekly administration of AMG 386 in combination with three common chemotherapy regimens was well tolerated in patients with advanced solid tumors. No pharmacokinetic interactions between AMG 386 and any of the tested chemotherapy regimens were noted. Promising antitumor activity was observed with all three treatment combinations. Clin Cancer Res; 16(11); 3044-56. (c)2010 AACR.
Phase 1 Study of AMG 386, a Selective Angiopoietin 1/2-Neutralizing Peptibody, in Combination with Chemotherapy in Adults with Advanced Solid Tumors.
Mita AC, Takimoto CH, Mita M, Tolcher A, Sankhala K, Sarantopoulos J, Valdivieso M, Wood L, Rasmussen E, Sun YN, Zhong ZD, Bass MB, Le N, Lorusso P.
Authors' Affiliations: Institute for Drug Development, San Antonio, Texas; Karmanos Cancer Institute, Detroit, Michigan; and Amgen, Inc., Thousand Oaks, California.
Abstract
PURPOSE: To evaluate the safety, pharmacokinetics, and antitumor activity of AMG 386, an investigational selective angiopoietin 1/2-neutralizing peptibody, in combination with FOLFOX-4 (F), carboplatin/paclitaxel (C/P), or docetaxel (D), in adult patients with advanced solid tumors. EXPERIMENTAL DESIGN: Three cohorts of patients (F, n = 6; C/P, n = 8; D, n = 12) received one full cycle of chemotherapy alone during the pretreatment phase, followed by administration of AMG 386 10 mg/kg i.v. weekly in combination with chemotherapy until disease progression or intolerance. Safety and tolerability, tumor response, pharmacokinetic profiles, and biomarkers were assessed. RESULTS: Twenty-six patients were enrolled; 22 received treatment with AMG 386. No dose-limiting toxicities or grade 3 or 4 adverse events related to AMG 386 were reported. The most common adverse events were diarrhea and hypomagnesemia (n = 3 each). One patient developed grade 2 hypertension and one had grade 1 subconjunctival eye hemorrhage. No neutralizing antibodies to AMG 386 were detected. There were no pharmacokinetic interactions between AMG 386 and F, C/P, or D. One patient receiving AMG 386 plus C/P for bladder cancer refractory to gemcitabine/cisplatin had a complete response at week 8. The remaining best tumor responses were partial response (n = 3, one from each cohort), stable disease >/=8 weeks (n = 13), and progressive disease (n = 1). CONCLUSIONS: Weekly administration of AMG 386 in combination with three common chemotherapy regimens was well tolerated in patients with advanced solid tumors. No pharmacokinetic interactions between AMG 386 and any of the tested chemotherapy regimens were noted. Promising antitumor activity was observed with all three treatment combinations. Clin Cancer Res; 16(11); 3044-56. (c)2010 AACR.
CARBOPALTIN PLUS CAELYX FOR PLATINUM SENSITIVE OVARIAN CANCER
J Clin Oncol. 2010 May 24. [Epub ahead of print]
Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse.
Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A.
University Paris Descartes, Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel-Dieu; Association de Recherche sur les Cancers dont Gynécologiques Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens, Paris; Centre Catherine De Sienne, Nantes; Centre Hospitalier Universitaire-Centre François Baclesse, Caen, France; Philipps University Marburg, Marburg; University Hospital Charité/Campus Virchow-Klinikum, Berlin; Klinikum Offenbach, Offenbach; Dr Horst Schmidt Klinik, Wiesbaden, Germany; Karolinska University Hospital and Karolinska Institutet Stockholm, Sweden; NHMRC Clinical Trials Centre, Sydney, New South Wales; University of Queensland, Brisbane, Queensland, Australia; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Medical University Innsbruck, Innsbruck, Austria; University Hospital Leuven, Leuven, Belgium; National Cancer Institute, Naples; Academic Division of Gynecological Oncology, Institute for Cancer Research and Treatment of Candiolo & Azienda Ospedaliera Ordine Mauriziano, Turin, Italy; and Norwegian Radium Hospital, Oslo, Norway.
Abstract
PURPOSE This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC). PATIENTS AND METHODS Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m(2)) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m(2)) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival. Results Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm. CONCLUSION To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.
Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse.
Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A.
University Paris Descartes, Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel-Dieu; Association de Recherche sur les Cancers dont Gynécologiques Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens, Paris; Centre Catherine De Sienne, Nantes; Centre Hospitalier Universitaire-Centre François Baclesse, Caen, France; Philipps University Marburg, Marburg; University Hospital Charité/Campus Virchow-Klinikum, Berlin; Klinikum Offenbach, Offenbach; Dr Horst Schmidt Klinik, Wiesbaden, Germany; Karolinska University Hospital and Karolinska Institutet Stockholm, Sweden; NHMRC Clinical Trials Centre, Sydney, New South Wales; University of Queensland, Brisbane, Queensland, Australia; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Medical University Innsbruck, Innsbruck, Austria; University Hospital Leuven, Leuven, Belgium; National Cancer Institute, Naples; Academic Division of Gynecological Oncology, Institute for Cancer Research and Treatment of Candiolo & Azienda Ospedaliera Ordine Mauriziano, Turin, Italy; and Norwegian Radium Hospital, Oslo, Norway.
Abstract
PURPOSE This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC). PATIENTS AND METHODS Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m(2)) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m(2)) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival. Results Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm. CONCLUSION To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.
BEVACIZUMAB AND DOCETAXEL FOR METASTATIC BREAST CANCER
J Clin Oncol. 2010 May 24. [Epub ahead of print]
Phase III Study of Bevacizumab Plus Docetaxel Compared With Placebo Plus Docetaxel for the First-Line Treatment of Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer.
Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G.
Abstract
PURPOSE The efficacy and safety of combining bevacizumab (7.5 and 15 mg/kg) with docetaxel as first-line therapy for human epidermal growth factor receptor 2 (HER2) -negative, locally recurrent or metastatic breast cancer (MBC) was investigated in a three-arm, placebo-controlled, phase III trial. PATIENTS AND METHODS Patients (N = 736) were randomly assigned to docetaxel 100 mg/m(2) plus either placebo or bevacizumab 7.5 or 15 mg/kg every 3 weeks. The primary end point was progression-free survival (PFS); secondary end points included best overall response, duration of response, time to treatment failure, overall survival, and safety. Results Combination of bevacizumab 15 mg/kg, but not 7.5 mg/kg, with docetaxel showed superior median PFS (mPFS) to placebo plus docetaxel in unstratified analysis (placebo mPFS, 8.2 months; 7.5 mg/kg mPFS, 9.0 months [hazard ratio (HR), 0.86; P = .12]; 15 mg/kg mPFS, 10.1 months [HR, 0.77; P = .006]) and stratified analysis (placebo mPFS, 8.1 months; 7.5 mg/kg mPFS, 9.0 months [HR, 0.80; P = .045]; 15 mg/kg mPFS, 10.0 months [HR, 0.67; P < .001]). Response rates in patients with measurable disease at baseline also increased with bevacizumab 15 mg/kg (46% [placebo] v 55% [7.5 mg/kg; P = .07] and 64% [15 mg/kg; P < .001]). Combination with bevacizumab had limited impact on the known toxicity profile of docetaxel. CONCLUSION Combination of bevacizumab with docetaxel did not significantly impact on the safety profile of docetaxel. Bevacizumab 15 mg/kg every 3 weeks significantly increased PFS when combined with docetaxel as first-line therapy for MBC compared with docetaxel plus placebo.
Phase III Study of Bevacizumab Plus Docetaxel Compared With Placebo Plus Docetaxel for the First-Line Treatment of Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer.
Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G.
Abstract
PURPOSE The efficacy and safety of combining bevacizumab (7.5 and 15 mg/kg) with docetaxel as first-line therapy for human epidermal growth factor receptor 2 (HER2) -negative, locally recurrent or metastatic breast cancer (MBC) was investigated in a three-arm, placebo-controlled, phase III trial. PATIENTS AND METHODS Patients (N = 736) were randomly assigned to docetaxel 100 mg/m(2) plus either placebo or bevacizumab 7.5 or 15 mg/kg every 3 weeks. The primary end point was progression-free survival (PFS); secondary end points included best overall response, duration of response, time to treatment failure, overall survival, and safety. Results Combination of bevacizumab 15 mg/kg, but not 7.5 mg/kg, with docetaxel showed superior median PFS (mPFS) to placebo plus docetaxel in unstratified analysis (placebo mPFS, 8.2 months; 7.5 mg/kg mPFS, 9.0 months [hazard ratio (HR), 0.86; P = .12]; 15 mg/kg mPFS, 10.1 months [HR, 0.77; P = .006]) and stratified analysis (placebo mPFS, 8.1 months; 7.5 mg/kg mPFS, 9.0 months [HR, 0.80; P = .045]; 15 mg/kg mPFS, 10.0 months [HR, 0.67; P < .001]). Response rates in patients with measurable disease at baseline also increased with bevacizumab 15 mg/kg (46% [placebo] v 55% [7.5 mg/kg; P = .07] and 64% [15 mg/kg; P < .001]). Combination with bevacizumab had limited impact on the known toxicity profile of docetaxel. CONCLUSION Combination of bevacizumab with docetaxel did not significantly impact on the safety profile of docetaxel. Bevacizumab 15 mg/kg every 3 weeks significantly increased PFS when combined with docetaxel as first-line therapy for MBC compared with docetaxel plus placebo.
RERADIATING RECURRENT GLIOMAS IS EFFECTIVE
June 3, 2010 — Reradiating recurrent high-grade gliomas is a viable treatment strategy and could possibly be a standard salvage therapy in this setting, according to the authors of a new study.
Patients with recurrent high-grade gliomas who were treated with hypofractionated stereotactic radiation therapy (H-SRT) had survival rates that were comparable to the "best-reported results in the literature" for systemic agents, such as bevacizumab, according to the authors, led by Shannon Fogh, MD, from Thomas Jefferson University in Philadelphia, Pennsylvania.
In this study of 147 recurrent patients treated with H-SRT (median dose, 35.0 Gy in 3.5 Gy fractions), there was a median survival time of 11 months after the salvage H-SRT therapy, the authors report in their study, published online May 17 in the Journal of Clinical Oncology.
H-SRT also had "an improved toxicity profile and decreased cost," compared with systemic maintenance therapy with bevacizumab, which is approved by the US Food and Drug Administration for the treatment of recurrent glioblastomas, Dr. Fogh and coauthors point out.
They emphasize that their study was observational and that any comparisons between H-SRT and other therapies were based on published literature.
Nevertheless, the survival, toxicity, and cost data led the authors to conclude that H-SRT should be evaluated in future studies as the "standard salvage therapy for previously irradiated high-grade gliomas."
Dr. Fogh admitted that many clinicians might find this approach unpalatable.
"In the eyes of many patients, neuro-oncologists, and even radiation oncologists who do not treat a large volume of brain patients, the concept of brain re-irradiation, particularly with such large doses given to the area previously treated with radiation therapy, seems dangerous and prohibitive," she told Medscape Oncology.
However, this study, which is the largest series to date on this approach, might change a few minds, suggest the authors.
No standard of care exists in this setting, said Dr. Fogh, but bevacizumab is "commonly given."
"It is important to realize, however, that the population treated with bevacizumab and H-SRT is not always the same; larger and more infiltrative tumors are more likely to get the drug, and those more compact and less infiltrative, the H-SRT. Those 2 approaches to salvage can be looked at as complementary, at least in a proportion of patients," she explained.
Study Rationale and Design
H-SRT seems like a good approach in patients with recurrent gliomas because of "their grim prognosis," say the study authors.
"It is imperative to consider quality of life when evaluating treatment options," they note. Thus, the shorter treatment schedule with hypofractionation (2 weeks vs 3 or 4 weeks) is a plus, they suggest. Also, H-SRT allows for precise treatment and a possible reduction in toxicity.
The authors note that this approach makes economic sense — in a couple of ways.
"Although the cost of re-irradiation is already a fraction of the cost of systemic maintenance therapy, examination of Medicare reimbursement rates for H-SRT demonstrated a cost savings of 20% (i.e., $4498.07 compared with $5705.47) with 10 treatments, compared with the 18 treatments of a typical fractionation schedule," they explain.
With these thoughts in mind, the investigators designed the study.
All the study participants were diagnosed with recurrence on the basis of radiographically identified tumor progression. Clinical judgment was used to define eligibility for H-SRT, the authors explain.
At Thomas Jefferson University, patients are generally eligible for treatment if the tumor volume is within a 10 × 10 cm field, the Karnofsky performance score (KPS) is 60 or higher, and the patients are able to lie flat for treatment planning and delivery.
The 147 patients had either grade 3 astrocytoma (n = 42; 29%) or glioblastoma multiforme (n = 105; 71%), and all had clinical and radiographic evidence of tumor progression.
All patients were followed with magnetic resonance imaging scans, which were obtained 6 to 8 weeks after H-SRT and at 3-month intervals from then on.
All patients had received initial postoperative conformal fractionated radiotherapy to a median dose of 60 Gy in daily 2 Gy fractions.
In all, 110 patients received chemotherapy at the time of initial diagnosis, and 48 received chemotherapy at recurrence with H-SRT.
All patients underwent neurosurgical intervention at initial diagnosis, and 84 patients (60%) had resection at recurrence before salvage H-SRT.
"Overall, the groups with resection plus H-SRT and with H-SRT alone were balanced with respect to initial treatment regimen, time to progression, dose of re-irradiation, and presence of multiple lesions," summarize the authors.
Study Results
Using H-SRT in 3.5 Gy fractions to 35.0 Gy, the investigators reported no grade 3 toxicities or reoperation secondary to toxicity in the patients. This provides "additional support that this dose and fraction size is well tolerated," they write.
There was also no survival benefit when chemotherapy was added to the radiation, report the authors.
"Although it was not a randomized trial, our study did not demonstrate a survival advantage in combining chemotherapy with H-SRT at recurrence compared with patients who received H-SRT alone," they write.
Despite the variability of the participants, their initial treatments, and salvage therapies, the authors observe that "all groups of patients benefited similarly from H-SRT, achieving a uniform" median survival time of 11 months.
The researchers have disclosed no relevant financial relationships.
J Clin Oncol. Published online May 17, 2010. Abstract
Patients with recurrent high-grade gliomas who were treated with hypofractionated stereotactic radiation therapy (H-SRT) had survival rates that were comparable to the "best-reported results in the literature" for systemic agents, such as bevacizumab, according to the authors, led by Shannon Fogh, MD, from Thomas Jefferson University in Philadelphia, Pennsylvania.
In this study of 147 recurrent patients treated with H-SRT (median dose, 35.0 Gy in 3.5 Gy fractions), there was a median survival time of 11 months after the salvage H-SRT therapy, the authors report in their study, published online May 17 in the Journal of Clinical Oncology.
H-SRT also had "an improved toxicity profile and decreased cost," compared with systemic maintenance therapy with bevacizumab, which is approved by the US Food and Drug Administration for the treatment of recurrent glioblastomas, Dr. Fogh and coauthors point out.
They emphasize that their study was observational and that any comparisons between H-SRT and other therapies were based on published literature.
Nevertheless, the survival, toxicity, and cost data led the authors to conclude that H-SRT should be evaluated in future studies as the "standard salvage therapy for previously irradiated high-grade gliomas."
Dr. Fogh admitted that many clinicians might find this approach unpalatable.
"In the eyes of many patients, neuro-oncologists, and even radiation oncologists who do not treat a large volume of brain patients, the concept of brain re-irradiation, particularly with such large doses given to the area previously treated with radiation therapy, seems dangerous and prohibitive," she told Medscape Oncology.
However, this study, which is the largest series to date on this approach, might change a few minds, suggest the authors.
No standard of care exists in this setting, said Dr. Fogh, but bevacizumab is "commonly given."
"It is important to realize, however, that the population treated with bevacizumab and H-SRT is not always the same; larger and more infiltrative tumors are more likely to get the drug, and those more compact and less infiltrative, the H-SRT. Those 2 approaches to salvage can be looked at as complementary, at least in a proportion of patients," she explained.
Study Rationale and Design
H-SRT seems like a good approach in patients with recurrent gliomas because of "their grim prognosis," say the study authors.
"It is imperative to consider quality of life when evaluating treatment options," they note. Thus, the shorter treatment schedule with hypofractionation (2 weeks vs 3 or 4 weeks) is a plus, they suggest. Also, H-SRT allows for precise treatment and a possible reduction in toxicity.
The authors note that this approach makes economic sense — in a couple of ways.
"Although the cost of re-irradiation is already a fraction of the cost of systemic maintenance therapy, examination of Medicare reimbursement rates for H-SRT demonstrated a cost savings of 20% (i.e., $4498.07 compared with $5705.47) with 10 treatments, compared with the 18 treatments of a typical fractionation schedule," they explain.
With these thoughts in mind, the investigators designed the study.
All the study participants were diagnosed with recurrence on the basis of radiographically identified tumor progression. Clinical judgment was used to define eligibility for H-SRT, the authors explain.
At Thomas Jefferson University, patients are generally eligible for treatment if the tumor volume is within a 10 × 10 cm field, the Karnofsky performance score (KPS) is 60 or higher, and the patients are able to lie flat for treatment planning and delivery.
The 147 patients had either grade 3 astrocytoma (n = 42; 29%) or glioblastoma multiforme (n = 105; 71%), and all had clinical and radiographic evidence of tumor progression.
All patients were followed with magnetic resonance imaging scans, which were obtained 6 to 8 weeks after H-SRT and at 3-month intervals from then on.
All patients had received initial postoperative conformal fractionated radiotherapy to a median dose of 60 Gy in daily 2 Gy fractions.
In all, 110 patients received chemotherapy at the time of initial diagnosis, and 48 received chemotherapy at recurrence with H-SRT.
All patients underwent neurosurgical intervention at initial diagnosis, and 84 patients (60%) had resection at recurrence before salvage H-SRT.
"Overall, the groups with resection plus H-SRT and with H-SRT alone were balanced with respect to initial treatment regimen, time to progression, dose of re-irradiation, and presence of multiple lesions," summarize the authors.
Study Results
Using H-SRT in 3.5 Gy fractions to 35.0 Gy, the investigators reported no grade 3 toxicities or reoperation secondary to toxicity in the patients. This provides "additional support that this dose and fraction size is well tolerated," they write.
There was also no survival benefit when chemotherapy was added to the radiation, report the authors.
"Although it was not a randomized trial, our study did not demonstrate a survival advantage in combining chemotherapy with H-SRT at recurrence compared with patients who received H-SRT alone," they write.
Despite the variability of the participants, their initial treatments, and salvage therapies, the authors observe that "all groups of patients benefited similarly from H-SRT, achieving a uniform" median survival time of 11 months.
The researchers have disclosed no relevant financial relationships.
J Clin Oncol. Published online May 17, 2010. Abstract
DENOSUMAB APPROVED FOR OSTEOPOROSIS
June 2, 2010 — The US Food and Drug Administration (FDA) yesterday approved denosumab (Prolia; Amgen), an injectable drug for postmenopausal women with osteoporosis who are at high risk for fractures. This is the first new class of medicine for treating postmenopausal osteoporosis that has been approved in many years.
For postmenopausal osteoporosis, an injection of denosumab may be administered subcutaneously by a healthcare provider once every 6 months to reduce bone destruction and to improve bone mass and strength.
Women make up 80% of those with osteoporosis in the United States, and 1 of 2 women older than 50 years will have an osteoporotic fracture during their lifetime, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
"Due to its prevalence, osteoporosis is a serious concern to public health," Julie Beitz, MD, director of the FDA's Office of Drug Evaluation III, said in a news release. "The approval of Prolia provides another treatment option for postmenopausal women with osteoporosis who are susceptible to fractures."
Women with osteoporosis who are considered to be at high risk for fracture include those with previous osteoporotic fracture or multiple risk factors for fracture or those who have failed or are intolerant to other available treatment of osteoporosis.
In a 3-year, randomized, double-blind, placebo-controlled trial (Fracture REduction Evaluation of Denosumab in Osteoporosis every six Months [FREEDOM]) enrolling 7808 postmenopausal women aged 60 to 91 years, denosumab was associated with lower incidence of vertebral, nonvertebral, and hip fractures in women with osteoporosis.
The drug was administered as a 60-mg subcutaneous injection every 6 months vs placebo at 3 years. The trial resulted in a 68% reduction in vertebral fractures, 40% reduction in hip fractures, 20% reduction in nonvertebral fractures, and significant increases in bone density at the lumbar spine, total hip, and femoral neck.
Back pain, limb pain, musculoskeletal pain, hypercholesterolemia, and urinary bladder infections were the most common adverse effects reported with denosumab. Serious adverse events included hypocalcemia, serious skin and other infections, and dermatologic conditions including dermatitis, rashes, and eczema.
Denosumab is contraindicated in patients with hypocalcemia and may worsen particularly in patients with severe renal impairment. These patients should receive a supplement of calcium and vitamin D.
Because denosumab significantly suppresses bone turnover, it may increase risk for osteonecrosis of the jaw, atypical fractures, and delayed fracture healing. The FDA therefore requires a risk evaluation and mitigation strategy (REMS), including a medication guide for patients and information for healthcare providers regarding the risks and benefits of denosumab.
For postmenopausal osteoporosis, an injection of denosumab may be administered subcutaneously by a healthcare provider once every 6 months to reduce bone destruction and to improve bone mass and strength.
Women make up 80% of those with osteoporosis in the United States, and 1 of 2 women older than 50 years will have an osteoporotic fracture during their lifetime, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
"Due to its prevalence, osteoporosis is a serious concern to public health," Julie Beitz, MD, director of the FDA's Office of Drug Evaluation III, said in a news release. "The approval of Prolia provides another treatment option for postmenopausal women with osteoporosis who are susceptible to fractures."
Women with osteoporosis who are considered to be at high risk for fracture include those with previous osteoporotic fracture or multiple risk factors for fracture or those who have failed or are intolerant to other available treatment of osteoporosis.
In a 3-year, randomized, double-blind, placebo-controlled trial (Fracture REduction Evaluation of Denosumab in Osteoporosis every six Months [FREEDOM]) enrolling 7808 postmenopausal women aged 60 to 91 years, denosumab was associated with lower incidence of vertebral, nonvertebral, and hip fractures in women with osteoporosis.
The drug was administered as a 60-mg subcutaneous injection every 6 months vs placebo at 3 years. The trial resulted in a 68% reduction in vertebral fractures, 40% reduction in hip fractures, 20% reduction in nonvertebral fractures, and significant increases in bone density at the lumbar spine, total hip, and femoral neck.
Back pain, limb pain, musculoskeletal pain, hypercholesterolemia, and urinary bladder infections were the most common adverse effects reported with denosumab. Serious adverse events included hypocalcemia, serious skin and other infections, and dermatologic conditions including dermatitis, rashes, and eczema.
Denosumab is contraindicated in patients with hypocalcemia and may worsen particularly in patients with severe renal impairment. These patients should receive a supplement of calcium and vitamin D.
Because denosumab significantly suppresses bone turnover, it may increase risk for osteonecrosis of the jaw, atypical fractures, and delayed fracture healing. The FDA therefore requires a risk evaluation and mitigation strategy (REMS), including a medication guide for patients and information for healthcare providers regarding the risks and benefits of denosumab.
SEQUENTIAL CHEMOTHERAPY MORE EFFECTIVE IN BREAST CANCER
June 3, 2010 — The sequential administration of chemotherapy was more effective than concurrent administration in women with operable node-positive breast cancer. The sequential ACT regimen — doxorubicin (Adriamycin) and cyclophosphamide followed by docetaxel (Taxotere) — had a greater impact on disease-free survival than a doxorubicin/docetaxel combination or concurrent ACT.
According to a study published in the June 3 issue of the New England Journal of Medicine, the sequential administration of ACT provided a significant 17% reduction in mortality, compared with doxorubicin/docetaxel treatment (P = .03). It also showed a nonsignificant 14% reduction in mortality compared with concurrent ACT (P = .09).
Disease-free survival was also better with sequential ACT than with the 2 other therapeutic regimens, and the authors note that their results suggest that a shorter course of treatment is not as effective as a longer one.
However, in an accompanying editorial, Matthew Ellis, BChir, PhD, professor of medicine at Washington University School of Medicine in St. Louis, Missouri, points out that the conclusion that a longer duration of treatment is better "should not be considered a general principle, but rather a product of the unbalanced design of the study."
The study, the National Surgical Adjuvant Breast and Bowel Project B-30 trial, was developed to identify a short-course, taxane-based chemotherapy regimen for patients with node-positive breast cancer. Some of the results were presented in 2008 at the San Antonio Breast Cancer Symposium, and were reported by Medscape Oncology at that time.
Longer Regiment Not Necessarily Superior
The study compared 3 regimens in patients with operable early-stage node-positive disease: 4 cycles of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT); a similar 12-week regimen with just doxorubicin and docetaxel; and a 24-week regimen in which docetaxel was administered separately from the doxorubicin/cyclophosphamide combination (sequential ACT).
The primary goals of the study were to assess whether concurrent ACT is more effective than sequential ACT, and if a doxorubicin/docetaxel regimen is as effective as concurrent ACT.
It is only in the context of this trial that longer regimens are better, explained Dr. Ellis; there have been other trials where shorter regimens were more effective, such as the CALGB 9741 trial.
CALGB 9741 supported the principle of dose density; the shorter regimens offer the same drug dose but in a more condensed period of time. That was not the case in this trial, he told Medscape Oncology.
As Dr. Ellis notes in his editorial, "it is hard to escape the conclusion that the inferior results associated with the 12-week regimens in this trial were mainly due to the significant dose reductions required to make the doxorubicin–docetaxel and concurrent-ACT regimens feasible."
"You simply can't force 3 drugs together and expect to give them at the regular dose," he said. "Giving myelosuppressive drugs at the same time almost always increases the side effects, and you have to lower the doses."
To accurately compare regimens of different lengths, the same drugs need to be given at the same dose, Dr. Ellis said. "This trial was not designed to establish any kind of principle."
He also wonders why the drugs were given concurrently in the first place. "This was never made clear, and there is no evidence that there is any sort of synergy between them," Dr. Ellis explained. "We shouldn't put drugs together just to do it. If you put together a combination, then there has to be rationale behind it."
Ovarian Suppression or Toxicity
Another result from the study is that patients who developed amenorrhea that lasted at least 6 months had better overall survival. This was the case across all treatment groups, independent of estrogen-receptor (ER) status. It had been thought that the value of ovarian suppression was restricted to ER-positive disease, and the study authors write that this is one of the "most intriguing findings of this trial."
Although ovarian ablation has been associated with an improved outcome in premenopausal women, Dr. Ellis pointed out that "direct ovarian suppression with a drug or surgery is not the same thing as ovarian toxicity from chemotherapy."
"It could be that the women who are going into menopause are experiencing more toxicity, and that is why they are getting the dose effect," he said. "They are metabolizing the drug more slowly, and therefore getting a higher dose and an enhanced clinical effect."
Dr. Ellis notes that ovarian suppression could also alter the clinical course of ER-negative disease, which might account for the benefit seen in both ER-positive and ER-negative patients. "Ovarian surgery appears to reduce the risk of breast cancer among carriers of the breast-cancer susceptibility gene BRCA1, in whom ER-negative and HER2-negative disease is the predominant presentation," he writes. It might be that ovarian suppression alters tumor progression in ER-negative disease indirectly, possibly through the tumor microenvironment.
Study Details
In this study, Sandra M. Swain, MD, from Washington Hospital Center in the District of Columbia, and colleagues randomized 5351 patients with operable, node-positive, early-stage breast cancer to 1 of the 3 trial groups.
At a median follow-up of 73 months, the authors observed that overall survival was better with sequential ACT (8-year overall survival, 83%), than with doxorubicin/docetaxel (overall survival, 79%; hazard ratio [HR] for death, 0.83; P = .03) and concurrent ACT (overall survival, 79%; HR, 0.86; P = .09).
Disease-free survival was also better with sequential ACT (8-year disease-free survival, 74%) than with doxorubicin/docetaxel (69%; HR for recurrence, a second malignant condition, or death, 0.80; P = .001) and concurrent ACT (69%; HR, 0.83; P = .01).
Doxorubicin/docetaxel showed noninferiority to concurrent ACT for overall survival (HR, 0.96; 95% confidence interval, 0.82 - 1.14).
As far as toxicity, patients receiving sequential ACT had a higher incidence of grade 3 or 4 adverse events (65%) than 45% of patients receiving doxorubicin/docetaxel and 48% of patients receiving concurrent ACT. Sequential ACT was also associated with significant increases in stomatitis, febrile neutropenia, and infection, compared with the other therapies, and arthralgia, fatigue, and vomiting were reported less frequently with doxorubicin/docetaxel.
There were 5 treatment-related deaths with sequential ACT (<1%), 7 with doxorubicin/docetaxel (<1%), and 12 with concurrent ACT (<1%).
The study was funded by Public Health Service grants from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services; and by Sanofi-Aventis. The study authors report a number of financial relationships, as detailed in the paper. Dr. Ellis reports consulting for Bristol-Myers Squibb, Sanofi-Aventis, Novartis, Pfizer, AstraZeneca, Abraxis, and GlaxoSmithKline.
N Engl J Med. 2010;362:2053-2065.
According to a study published in the June 3 issue of the New England Journal of Medicine, the sequential administration of ACT provided a significant 17% reduction in mortality, compared with doxorubicin/docetaxel treatment (P = .03). It also showed a nonsignificant 14% reduction in mortality compared with concurrent ACT (P = .09).
Disease-free survival was also better with sequential ACT than with the 2 other therapeutic regimens, and the authors note that their results suggest that a shorter course of treatment is not as effective as a longer one.
However, in an accompanying editorial, Matthew Ellis, BChir, PhD, professor of medicine at Washington University School of Medicine in St. Louis, Missouri, points out that the conclusion that a longer duration of treatment is better "should not be considered a general principle, but rather a product of the unbalanced design of the study."
The study, the National Surgical Adjuvant Breast and Bowel Project B-30 trial, was developed to identify a short-course, taxane-based chemotherapy regimen for patients with node-positive breast cancer. Some of the results were presented in 2008 at the San Antonio Breast Cancer Symposium, and were reported by Medscape Oncology at that time.
Longer Regiment Not Necessarily Superior
The study compared 3 regimens in patients with operable early-stage node-positive disease: 4 cycles of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT); a similar 12-week regimen with just doxorubicin and docetaxel; and a 24-week regimen in which docetaxel was administered separately from the doxorubicin/cyclophosphamide combination (sequential ACT).
The primary goals of the study were to assess whether concurrent ACT is more effective than sequential ACT, and if a doxorubicin/docetaxel regimen is as effective as concurrent ACT.
It is only in the context of this trial that longer regimens are better, explained Dr. Ellis; there have been other trials where shorter regimens were more effective, such as the CALGB 9741 trial.
CALGB 9741 supported the principle of dose density; the shorter regimens offer the same drug dose but in a more condensed period of time. That was not the case in this trial, he told Medscape Oncology.
As Dr. Ellis notes in his editorial, "it is hard to escape the conclusion that the inferior results associated with the 12-week regimens in this trial were mainly due to the significant dose reductions required to make the doxorubicin–docetaxel and concurrent-ACT regimens feasible."
"You simply can't force 3 drugs together and expect to give them at the regular dose," he said. "Giving myelosuppressive drugs at the same time almost always increases the side effects, and you have to lower the doses."
To accurately compare regimens of different lengths, the same drugs need to be given at the same dose, Dr. Ellis said. "This trial was not designed to establish any kind of principle."
He also wonders why the drugs were given concurrently in the first place. "This was never made clear, and there is no evidence that there is any sort of synergy between them," Dr. Ellis explained. "We shouldn't put drugs together just to do it. If you put together a combination, then there has to be rationale behind it."
Ovarian Suppression or Toxicity
Another result from the study is that patients who developed amenorrhea that lasted at least 6 months had better overall survival. This was the case across all treatment groups, independent of estrogen-receptor (ER) status. It had been thought that the value of ovarian suppression was restricted to ER-positive disease, and the study authors write that this is one of the "most intriguing findings of this trial."
Although ovarian ablation has been associated with an improved outcome in premenopausal women, Dr. Ellis pointed out that "direct ovarian suppression with a drug or surgery is not the same thing as ovarian toxicity from chemotherapy."
"It could be that the women who are going into menopause are experiencing more toxicity, and that is why they are getting the dose effect," he said. "They are metabolizing the drug more slowly, and therefore getting a higher dose and an enhanced clinical effect."
Dr. Ellis notes that ovarian suppression could also alter the clinical course of ER-negative disease, which might account for the benefit seen in both ER-positive and ER-negative patients. "Ovarian surgery appears to reduce the risk of breast cancer among carriers of the breast-cancer susceptibility gene BRCA1, in whom ER-negative and HER2-negative disease is the predominant presentation," he writes. It might be that ovarian suppression alters tumor progression in ER-negative disease indirectly, possibly through the tumor microenvironment.
Study Details
In this study, Sandra M. Swain, MD, from Washington Hospital Center in the District of Columbia, and colleagues randomized 5351 patients with operable, node-positive, early-stage breast cancer to 1 of the 3 trial groups.
At a median follow-up of 73 months, the authors observed that overall survival was better with sequential ACT (8-year overall survival, 83%), than with doxorubicin/docetaxel (overall survival, 79%; hazard ratio [HR] for death, 0.83; P = .03) and concurrent ACT (overall survival, 79%; HR, 0.86; P = .09).
Disease-free survival was also better with sequential ACT (8-year disease-free survival, 74%) than with doxorubicin/docetaxel (69%; HR for recurrence, a second malignant condition, or death, 0.80; P = .001) and concurrent ACT (69%; HR, 0.83; P = .01).
Doxorubicin/docetaxel showed noninferiority to concurrent ACT for overall survival (HR, 0.96; 95% confidence interval, 0.82 - 1.14).
As far as toxicity, patients receiving sequential ACT had a higher incidence of grade 3 or 4 adverse events (65%) than 45% of patients receiving doxorubicin/docetaxel and 48% of patients receiving concurrent ACT. Sequential ACT was also associated with significant increases in stomatitis, febrile neutropenia, and infection, compared with the other therapies, and arthralgia, fatigue, and vomiting were reported less frequently with doxorubicin/docetaxel.
There were 5 treatment-related deaths with sequential ACT (<1%), 7 with doxorubicin/docetaxel (<1%), and 12 with concurrent ACT (<1%).
The study was funded by Public Health Service grants from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services; and by Sanofi-Aventis. The study authors report a number of financial relationships, as detailed in the paper. Dr. Ellis reports consulting for Bristol-Myers Squibb, Sanofi-Aventis, Novartis, Pfizer, AstraZeneca, Abraxis, and GlaxoSmithKline.
N Engl J Med. 2010;362:2053-2065.
RADIATION METHODS IN HEAD AND NECK CANCER
June 1, 2010 — Intensity-modulated radiation therapy (IMRT) for head and neck cancer leads to fewer cases of xerostomia, but has not yet been proven to be more successful than any other kind of radiation therapy in reducing tumors or improving survival, according to a new comparative-effectiveness review funded by the federal Agency for Healthcare Research and Quality (AHRQ).
The review compares the effectiveness of 4 types of radiotherapy (IMRT, 3DCRT, 2DRT, and proton-beam therapy) in terms of tumor control, overall survival, adverse events, and quality-of-life issues.
Many scientists consider IMRT to be theoretically better able to target cancerous cells while sparing healthy tissue than either 3DCRT or 2DRT, but more research is needed, the authors of the report point out.
The report, entitled Comparative Effectiveness and Safety of Radiotherapy Treatments for Head and Neck Cancer, is authored by the Blue Cross and Blue Shield Association's Technology Evaluation Center Evidence-Based Practice Center.
The late adverse effect of xerostomia, also known as dry mouth, is less common than in the past because the use of IMRT has allowed radiation oncologists to spare most patients' salivary glands from radiation as part of treatment planning, an expert recently told Medscape Oncology.
Sparing salivary glands has become standard among clinicians who use IMRT, said Avraham Eisbruch, MD, professor of radiation oncology at the University of Michigan Medical School and Comprehensive Cancer Center in Ann Arbor.
Dr. Eisbruch's comments came in the context of his study on the use of IMRT to reduce dysphagia in head and neck cancer. However, he also served on the technical expert panel of the new comparative-effectiveness report.
According to the report, it is not known whether IMRT is better or worse at reducing the size of tumors, or whether it improves other outcome measures.
"Inconsistent and nonsignificant results were observed between IMRT and comparators on other adverse events, overall quality of life, tumor control, and survival outcomes. Thus, the evidence is insufficient to support conclusions in these areas," reads the report.
Overall, the report suffered from a lack of data with which to do comparisons, suggest the authors.
"A small body of randomized, controlled trials is accompanied by a larger body of poor quality observational, nonrandomized studies," they write about the evidence on the topic.
What About Proton-Beam Therapy?
The main focus of the report was IMRT. An informal survey estimates that 30% to 60% of all patients in the United States are treated with IMRT.
The report authors note that "most of the studies in this review were based on the results of patients treated at academic medical centers."
Because IMRT is increasingly adopted in community settings, the authors wonder whether results in head and neck cancer will continue to be the same.
"Whether similar results will be achieved as the technology diffuses to less-experienced settings has not been addressed in the comparative studies available for this review," they write.
The authors sought to examine the evidence regarding proton beam radiation therapy, but there were no head-to-head comparisons to review.
"The strength of evidence is insufficient, as there were no studies comparing proton-beam therapy to any other radiotherapy modality. Therefore, no conclusions can be reached regarding the comparative effectiveness of proton-beam therapy," write the authors.
Proton-beam radiation therapy is more commonly used to treat prostate cancer and pediatric tumors, the report notes.
In an AHRQ Technical Brief published last fall, researchers found limited evidence with which to determine whether proton-beam radiation therapy is safer or more effective than other types of radiation to treat cancer, according to AHRQ press materials.
The new comparative-effectiveness report is the latest research review from the AHRQ's Effective Health Care Program, which is an effort to compare alternative treatments for health conditions and to make the findings public, to help doctors, nurses, pharmacists, and others work together with patients to choose the most effective treatments.
The authors are employees of Blue Cross and Blue Shield.
The review compares the effectiveness of 4 types of radiotherapy (IMRT, 3DCRT, 2DRT, and proton-beam therapy) in terms of tumor control, overall survival, adverse events, and quality-of-life issues.
Many scientists consider IMRT to be theoretically better able to target cancerous cells while sparing healthy tissue than either 3DCRT or 2DRT, but more research is needed, the authors of the report point out.
The report, entitled Comparative Effectiveness and Safety of Radiotherapy Treatments for Head and Neck Cancer, is authored by the Blue Cross and Blue Shield Association's Technology Evaluation Center Evidence-Based Practice Center.
The late adverse effect of xerostomia, also known as dry mouth, is less common than in the past because the use of IMRT has allowed radiation oncologists to spare most patients' salivary glands from radiation as part of treatment planning, an expert recently told Medscape Oncology.
Sparing salivary glands has become standard among clinicians who use IMRT, said Avraham Eisbruch, MD, professor of radiation oncology at the University of Michigan Medical School and Comprehensive Cancer Center in Ann Arbor.
Dr. Eisbruch's comments came in the context of his study on the use of IMRT to reduce dysphagia in head and neck cancer. However, he also served on the technical expert panel of the new comparative-effectiveness report.
According to the report, it is not known whether IMRT is better or worse at reducing the size of tumors, or whether it improves other outcome measures.
"Inconsistent and nonsignificant results were observed between IMRT and comparators on other adverse events, overall quality of life, tumor control, and survival outcomes. Thus, the evidence is insufficient to support conclusions in these areas," reads the report.
Overall, the report suffered from a lack of data with which to do comparisons, suggest the authors.
"A small body of randomized, controlled trials is accompanied by a larger body of poor quality observational, nonrandomized studies," they write about the evidence on the topic.
What About Proton-Beam Therapy?
The main focus of the report was IMRT. An informal survey estimates that 30% to 60% of all patients in the United States are treated with IMRT.
The report authors note that "most of the studies in this review were based on the results of patients treated at academic medical centers."
Because IMRT is increasingly adopted in community settings, the authors wonder whether results in head and neck cancer will continue to be the same.
"Whether similar results will be achieved as the technology diffuses to less-experienced settings has not been addressed in the comparative studies available for this review," they write.
The authors sought to examine the evidence regarding proton beam radiation therapy, but there were no head-to-head comparisons to review.
"The strength of evidence is insufficient, as there were no studies comparing proton-beam therapy to any other radiotherapy modality. Therefore, no conclusions can be reached regarding the comparative effectiveness of proton-beam therapy," write the authors.
Proton-beam radiation therapy is more commonly used to treat prostate cancer and pediatric tumors, the report notes.
In an AHRQ Technical Brief published last fall, researchers found limited evidence with which to determine whether proton-beam radiation therapy is safer or more effective than other types of radiation to treat cancer, according to AHRQ press materials.
The new comparative-effectiveness report is the latest research review from the AHRQ's Effective Health Care Program, which is an effort to compare alternative treatments for health conditions and to make the findings public, to help doctors, nurses, pharmacists, and others work together with patients to choose the most effective treatments.
The authors are employees of Blue Cross and Blue Shield.
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