Κυριακή, 19 Νοεμβρίου 2017

NEW HYPERTENSION GUIDELINES

The American College of Cardiology (ACC) and the American Heart Association (AHA) have released a new guideline on hypertension with a new definition that will call 130 to 139 mm Hg systolic or 80 to 89 mm Hg stage 1 hypertension.
Officially the 2017 "ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults," the document includes new recommendations on the definition of hypertension, systolic and diastolic blood pressure thresholds for initiation of treatment with antihypertensive medications, and an aggressive new BP treatment target.
The guidelines were released here at the American Heart Association (AHA) 2017 Scientific Sessions and published simultaneously in the Journal of the American College of Cardiology[1], and in the AHA journal Hypertension[2].
"The goal was to provide a comprehensive guideline for diagnosis, prevention, evaluation, treatment, and very important, strategies to improve control rates during treatment," Dr Paul Whelton (Tulane University School of Public Health and Tropical Medicine, New Orleans, LA), chair of the 2017 Hypertension Practice Guidelines, told a press conference here.
Whelton pointed to five main areas of emphasis in the new guideline:
  • A strong emphasis on blood-pressure measurement, both accuracy of blood-pressure measurements and using the average of measures taken over several visits, as well as an emphasis on out-of-office blood-pressure measurements, "which is relatively new for a blood-pressure guideline," he noted.
  • A new blood-pressure classification system, updating the previous Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7) guidelines. "We thought the evidence supported a slightly new classification system," he said.
  • A new approach to decision-making for treatment that incorporates underlying cardiovascular risk.
  • Lower targets for blood pressure during the management of hypertension.
  • Strategies to improve blood-pressure control during treatment with an emphasis on lifestyle approaches.
    The writing committee didn't like the term prehypertension for patients particularly in that higher range, Whelton said, "because we felt at that stage somebody is already at substantial increased risk—double the risk for a heart attack compared with somebody in a normal blood-pressure range—so we think stage 1 hypertension is the appropriate term and that will capture the risk for adults and for clinicians much better."
     Blood Pressure Classification by JNC7 and 2017 ACC/AHA Hypertension Guidelines
    Systolic, Diastolic Blood Pressure (mm Hg)JNC72017 ACC/AHA 
    <120 and="" b="">Normal BPNormal BP
    120–129 and <80 b="">PrehypertensionElevated BP
    130–139 or 80–89 PrehypertensionStage 1 hypertension
    140–159 or 90–99Stage 1 hypertensionStage 2 hypertension
    > 160 or >100Stage 2 hypertensionStage 2 hypertension
    Whelton was also senior author on an accompanying study meant to look at the theoretical effects of the definitions and treatment goals in the new guideline[3] vs those set out in the previous JNC7 guideline.
    The study, with first author Dr Paul Munter (School of Public Health, University of Birmingham, Alabama), concludes that compared with the JNC7 guideline, the 2017 ACC/AHA guideline "results in a substantial increase in the prevalence of hypertension, but a small increase in the percentage of US adults recommended antihypertensive medication," adding that the 2017 ACC/AHA guidelines recommend that a substantial proportion of US adults taking antihypertensive medication be treated with more intensive BP lowering.
    Prevalence of Hypertension According to JNC7 and 2017 ACC/AHA Guidelines
    End Point JNC72017 ACC/AHA
    Prevalence of hypertension (%)31.945.6
    Number with hypertension (millions)72.2103.3
    The reason that prevalence will increase substantially but patients receiving treatment will only increase moderately is that the recommendations for stage 1 hypertension treatment are guided by the patients' underlying cardiovascular risk: only those with clinical cardiovascular disease or an estimated risk of 10% or more of atherosclerotic cardiovascular disease (ASCVD) would be offered treatment, and the remainder should be given advice on lifestyle modification.
    Vice-chair of the writing committee, Dr Robert M Carey (University of Virginia School of Medicine), discussed the committee's recommendations for treatment of hypertension.
    "Lifestyle modification is the cornerstone of the treatment of hypertension, and we expect that this guideline will cause our society and our physician community to really pay attention much more to lifestyle recommendations," Carey said during the briefing.
    Specific recommendations include advice to lose weight, follow a DASH-pattern diet, reduce sodium to less than 1500 mg/day and increase potassium intake to 3500 mg/day through dietary intake, increase physical activity to a minimum of 30 minutes of exercise three times per week, and limit alcohol intake to two drinks or less per day for men and one or less for women.
    Carey noted that they are recommending the ACC/AHA Pooled Cohort Equations to estimate the 10-year ASCVD risk, taking into account age, race, sex, total cholesterol, LDL cholesterol, HDL cholesterol, treatment with aspirin or a statin, systolic BP, treatment for hypertension, history of diabetes, and current smoking.
    Finally, he pointed to new goals for treatment of hypertension. "This has decreased since the last guideline," he noted. "The last guideline recommended less than 140/90 mm Hg; our guideline recommends a target of 130/80 mm Hg."
    Whelton discussed the rationale for this more intensive blood-pressure goal of less than 130/80 mm Hg in older adults. "It's largely based on the fact that a large number of older adults have been enrolled in blood-pressure–lowering treatment trials, especially in more recent trials," he said.
    In those studies, notably the SPRINT and ACCORD trials, antihypertensive treatment reduced CVD morbidity and mortality without any increased risk for falls or orthostatic hypotension.
    Thorough Review
    Moderating the press briefing this morning on the new guideline were Dr Stephen Hauser (Lewis Katz School of Medicine at Temple University, Philadelphia, PA), former president of the American Heart Association, standing in for current president Dr John J Warner (UT Southwestern University Hospitals, Dallas), and Dr Mary Walsh (St Vincent Heart Center of Indiana, Carmel), president of the American College of Cardiology.
    "We saw the need to update these guidelines to reflect the real threats of high blood pressure and establish a protocol that could improve the cardiovascular health of all Americans," Hauser said.
    "This guideline is the product of 3 years of thorough review by a panel of 21 experts who reviewed over 900 sources," he added. "The guidelines further underwent multiple rounds of peer review and were reviewed by the writing group of 41-member scientific advisory coordinating committee—which I'm a part of and I did read them—all partner organizations, and the guidelines executive committee."
    "We update guidelines based on evidence and continually monitor new research," Walsh commented. "The American Heart Association and the American College of Cardiology were given primary stewardship of the cardiovascular treatment guidelines from the US government in 2013. Shortly thereafter, the organizations began laying the groundwork for the new guideline, which has been in development now for 3 years.
    "Other groups have published high blood-pressure recommendations in the past 4 years, but they were not comprehensive, and they were not endorsed widely," she added. These guidelines, she said, "have been a collaborative effort by 11 organizations."
    Other partner organizations include the American Academy of Physician Assistants, the American College of Preventive Medicine, the American Geriatrics Society, the American Pharmacists Association, the American Society of Hypertension, the American Society of Preventive Cardiology, the Association of Black Cardiologists, the National Medical Association, and the Preventive Cardiovascular Nurses Association.

WARFARIN MAY PROTECT AGAINST CANCER DEVELOPMENT?

Use of the anticoagulant warfarin may protect against a broad range of cancers in people over age 50, according to a large observational study from Norway[1].
"We were surprised first by the breadth of the cancer-protective association, and second that this association was stronger in our subgroup analysis of patients taking warfarin for abnormal heart rhythms (atrial fibrillation or flutter)," Dr James B Lorens (University of Bergen, Norway) told theheart.org | Medscape Cardiology.
The findings "could have important implications for the selection of medications for patients needing anticoagulation," the researchers say.
The study was published online November 6, 2017 in JAMA Internal Medicine.

Implications for Switch to NOACS?

Among about 1.25 million adults aged 52 to 82 years identified in Norwegian national registries, 92,942 (7.4%) were classified as warfarin users and about 1.1 million were warfarin nonusers. Warfarin use was defined as taking at least 6 months of a warfarin prescription and at least 2 years from first prescription to any cancer diagnosis.
During the 7-year observation period, 132,687 participants (10.6%) were diagnosed with cancer. Compared with nonusers of warfarin, users of warfarin had significantly lower age- and sex-adjusted rates of all cancers and of cancer of the lung, prostate, and breast, but not the colon.
Incidence Rate Ratio of Cancer in Warfarin Users vs Nonusers
Cancer siteIRR (95% CI)
All cancers0.84 (0.82–0.86)
Prostate0.69 (0.65–0.72)
Lung0.80 (0.75–0.86)
Breast0.90 (0.82–1.00)
Colon0.99 (0.93–1.06)
A subgroup analysis of patients with atrial fibrillation or flutter showed significantly lower rates of cancer overall (IRR 0.62; 95% CI 0.59–0.65) and cancer of the lung (IRR 0.39, 95% CI 0.33–0.46), prostate (IRR 0.60, 95% CI 0.55–0.66), breast (0.72, 95% CI 0.59–0.87) and colon (IRR 0.71, 95% CI 0.63–0.81).
The association between warfarin use and lower cancer incidence in this subgroup was "stronger compared with that in groups in the main analysis," the researchers report.
They note that the "well-known challenges of warfarin dosing that necessitate regular monitoring have fueled a transition to new oral anticoagulants. An unintended consequence of this switch to new oral anticoagulants may be an increased incidence of cancer, which is an important consideration for public health," the authors write.
Σελίδα 2 από 2
Lorens cautioned that this was a large observational study using data from Norwegian national registries, which can't prove a cause-and-effect relationship, and there are significant limitations.
"However, preclinical studies show that warfarin has antitumor activity at doses that do not inhibit coagulation. This suggests that the antitumor effects of warfarin are not related to anticoagulation but rather are due to the vitamin K antagonist mechanism of action. We and others have shown in experimental cancer models that warfarin inhibits the activity of a receptor (AXL) found on tumor and immune cells. Studies are ongoing to better understand this mechanism," Lorens said.

"Important Study, Rigorous and Impactful"

"This is a very important study, rigorous and impactful," Dr Rolf A Brekken (UT Southwestern, Dallas), told theheart.org | Medscape Cardiology. "The team did a really nice job of breaking down the effect of warfarin on cancer incidence in the population. There are some confounders to the study; for instance . . . it is likely that this cohort of patients probably are not smokers, so that would also affect cancer incidence," he said.
"However, the data are a strong indicator that warfarin reduces cancer development," Brekken said, "and support preclinical work from my group that warfarin inhibits cancer metastasis in an AXL-dependent manner."
Brekken noted that his group and others have shown that low-dose warfarin doses that do not affect coagulation are capable of inhibiting AXL.
"This is exciting, as it suggests that you treat cancer patients with a low dose of warfarin, thereby reducing worries about toxicity, and have an anticancer benefit. This of course needs to be investigated in a clinical trial. Hopefully this will happen soon," Brekken said.
The study had no specific funding. Lorens reported ownership interest in BerGenBio ASA, which is developing AXL inhibitors. No other disclosures were reported.

COMBINATION THERAPY FOR LUNG-THYMUS CARCINOIDS

A European phase II trial has shown activity of long-acting pasireotide, everolimus (Afinitor), or their combination in patients with advanced lung and thymus carcinoids. These study findings were reported by Ferolla et al in The Lancet Oncology.
Study Details
In the study, 124 patients from 36 sites in 9 countries with unresectable or metastatic well-differentiated carcinoid tumors of the lung or thymus and radiologic disease progression within the prior 12 months were randomized between August 2013 and September 2014 to receive long-acting pasireotide at 60 mg intramuscularly every 28 days (n = 41), everolimus at 10 mg once daily (n = 42), or the combination (n = 41) for 12 months. Overall, 93% to 95% of patients across the groups had a carcinoid of the lung.
The primary endpoint was the proportion of patients who were progression free (complete or partial response or stable disease) at 9 months. The minimum number of patients required to be progression free at month 9 to consider the treatment effective was 13 in the pasireotide group, 14 in the everolimus group, and 13 in the combination group.
9-Month Outcome
At 9 months, the proportions of patients who were progression free were 39.0% (n = 16) in the long-acting pasireotide group, 33.3% (n = 14) in the everolimus group, and 58.5% (n = 24) in the combination group. No patients had a complete response, and partial response was observed in one patient in each group.
Adverse Events
The most common grade 3 or 4 adverse events suspected to be related to treatment were increased γ-glutamyltransferase (10%), diarrhea (7%), and hyperglycemia (7%) in the long-acting pasireotide group; hyperglycemia (17%), stomatitis (10%), and diarrhea (7%) in the everolimus group; and hyperglycemia (22%) and diarrhea (10%) in the combination group. Three deaths during or up to 56 days after the 12-month treatment phase were suspected to be related to everolimus: one in the everolimus group due to acute kidney injury associated with diarrhea, and two in the combination group, associated with diarrhea and urinary sepsis in one patient and acute renal failure and respiratory failure in one patient.
The investigators concluded: “The study met the primary endpoint in all three treatment groups. Safety profiles were consistent with the known safety profiles of these agents. Further studies are needed to confirm the antitumour efficacy of the combination of a somatostatin analogue with everolimus in lung and thymic carcinoids.”
The study was funded by Novartis Pharma AG.
Piero Ferolla, MD, of the Multidisciplinary NET Group, Umbria Regional Cancer Network and the University of Perugia, is the corresponding author of The Lancet Oncology article.

FAT CELLS MAY INACTIVATE CHEMOTHERAPY DRUGS

It is well established that obesity increases the risk for cancer mortality, although no mechanisms have been proven to explain the reason for this association. Now a laboratory study investigating how obesity might alter the effectiveness of daunorubicin in the treatment of acute lymphoblastic leukemia (ALL) is providing some clues. The study has found that adipocytes may metabolize and inactivate daunorubicin, reducing the active drug concentration in the tumor microenvironment and potentially contributing to poorer survival outcomes. The study’s finding could help explain why cancer patients with obesity are at risk of having a poorer outcome than their leaner counterparts and may have important implications across many diseases. The study by Sheng et al was published in Molecular Cancer Research.
Study Methodology
The researchers co-cultured human ALL cell lines with adipocytes and treated them with daunorubicin. They also studied whether human adipose tissue from patients with cancer, including adipose tissue biopsy samples from breast cancer survivors and bone marrow biopsy specimens from children aged 10 to 21 with high-risk ALL, could metabolize daunorubicin.
The researchers measured the presence of daunorubicin through flow cytometry and liquid chromatography/mass spectrometry and examined fat cells in bone marrow from the children with ALL.
Study Findings
The researchers made several key findings:
  • The presence of adipocytes significantly reduced the accumulation of daunorubicin in the ALL cells;
  • The adipocytes absorbed the chemotherapeutic agent, removing it from the leukemia environment. The leukemia cells treated with daunorubicin survived and proliferated better in samples that contained adipocytes;
  • The adipocytes metabolized daunorubicin. Enzymes in the fat cells changed the structure of the chemotherapy molecule, making it much less toxic to the leukemia cells.
“Specifically, adipocytes metabolize daunorubicin to a less toxic metabolite and allow nearby ALL cells to evade daunorubicin-induced cytotoxicity. This finding could help explain why obese cancer patients are at risk of having a poorer outcome. Pharmacokinetic studies specifically in the tumor microenvironment will be necessary to determine the precise impact of adiposity on anthracycline-based treatment and efficacy in patients with ALL and other cancers,” concluded the study authors.
“The finding that human fat cells can metabolize and inactivate a chemotherapy is novel and surprising,” said Steven Mittelman, MD, PhD, Associate Professor of Pediatrics and the Division Chief of Pediatric Endocrinology at UCLA Mattel Children’s Hospital in Los Angeles, and a coauthor of this study, in a statement. “This is important for leukemia and a lot of other cancers that grow in the bone marrow or around fat cells, since that means that fat cells might remove chemotherapy from the environment and allow the cancer cells to survive.”

SEX ONLY RARELY CAUSE CARDIAC ARREST

 Sexual activity is rarely the cause of sudden cardiac arrest, a new study suggests[1].
Specifically, in more than 4500 cases of sudden cardiac arrest in adults living in Portland, OR in a recent decade, only 34 cases were related to sexual activity within the preceding hour.
Sexual-activity–related sudden cardiac arrest occurred in 32 men and two women. That is, one in 100 cardiac arrests in men and one in 1000 cardiac arrests in women were related to sexual activity, the researchers report.
The study by Dr Aapo Aro (Cedars-Sinai Heart Institute, Los Angeles, CA) and colleagues were presented as a poster on November 12, 2017 at the American Heart Association (AHA) 2017 Scientific Sessions and simultaneously published in a research letter in the Journal of the American College of Cardiology.
"These findings are reassuring" for clinicians and provide data to help inform discussions with patients, senior author Dr Sumeet S Chugh (Cedars-Sinai Medical Center) told theheart.org | Medscape Cardiology in an email.
Clinicians can now "base their reassurance to heart-disease patients across the spectrum on actual data," he said.
Even though the cases of sudden cardiac arrest were witnessed by the sexual partners, only a third of the individuals received bystander CPR from their partners, which may explain why only about one in five individuals survived until hospital discharge.
The findings reinforce the continued need "to educate the public on the importance of bystander CPR," the researchers note.
Clinicians have known for some time that the risk of cardiac arrest is low during sexual activity, but patients remain concerned and may not bring up the subject during a visit to their doctor, AHA spokesperson Dr Nieca Goldberg (NYU School of Medicine, New York) told theheart.org | Medscape Cardiology.
"Sexual activity is the equivalent of climbing two flights of stairs," she noted. Patients who have had heart surgery or a heart attack tell her that they are concerned about resuming sexual activity, often based on what they see in movies such as Something's Gotta Give, where Jack Nicholson has sexual-activity–related heart attack.
She says its important for clinicians as well as patients to make sure that a discussion about resuming sexual activity is a part of the predischarge educational package "and certainly in the first follow-up visit" after cardiac surgery or an MI, she said. "We really need to get the message out about learning how to do CPR."

Health and Mortality Benefits vs Risk of Arrest

Sexual activity is an important aspect of quality of life and brings health and mortality benefits; however, there is no information on sexual activity as a potential trigger for sudden cardiac arrest in the general population, Aro and colleagues write.
For this report, they analyzed data from individuals living in Portland who had a sudden cardiac arrest during 2002 to 2012 and were part of the Oregon Sudden Unexpected Death Study.
All cases were adjudicated, and the researchers also had information about the circumstances surrounding the cardiac arrest, the patient's medical records over a lifetime, and autopsy data.
On average, compared with the 4523 cases of other types of sudden cardiac arrest, the 34 patients who had sexual-activity–related cardiac arrest were younger (mean age 60 vs 65; age range 34–83) and more likely to be male (94% vs 68%) or African American (19% vs 8%).
Cardiac disease was similar in both groups: about 29% of patients had a history of coronary artery disease, 26% had symptomatic heart failure, and most were taking cardiovascular medications.
Compared with patients with other types of cardiac arrest, those with sexual-activity–related cardiac arrest were more likely to present with ventricular fibrillation or tachycardia (76% vs 45%; P<0 .001="" p="">
Survival was greater after sexual-activity–related cardiac arrest, but this was not significant (19% vs 13%, P=0.29) and was likely due to different rates of shockable rhythms.
The study shows the need to "increase awareness and education of CPR even in this awkward situation," Chugh said.
The study was funded by National Heart, Lung, and Blood Institute grants to Chugh. Chugh has received grants from Boston Scientific and Medtronic. Aro and the other coauthors have no relevant financial relationships.

NEWER DRUGS IMPROVED SURVIVAL IN PROSTATE CANCER

Contemporary management of metastatic prostate cancer (mPCa) with any of the newer systemic agents that have been approved for castrate-resistant prostate cancer significantly prolongs both cancer-specific and overall survival compared with historical controls, the first population-based study of its kind suggests.
"A population-based study represents the most reliable option for identifying the real effect related to the examined treatment on the overall population," lead author Marco Bandini, MD, Osperdale San Raffaela, Milan, Italy, told Medscape Medical News in an email.
"Our study should encourage urologists and oncologists to intensify the use of such agents in this setting," he added.
The findings were published online November 11 in International Urology and Nephrology.
For their study, Dr Bandini and colleagues analyzed data from the Surveillance Epidemiology and End Results database for 2004 to 2014.
A total of 19,047 men who had been diagnosed with de novo mPCa were identified during the decade-long study interval.
Of this cohort, 4298 patients who received a diagnosis of mPCa between 2004 and 2008 were classified as historical control patients; 4298 men who were diagnosed with mPCa between 2009 and 2014 were classified as contemporary patients.
Because of potentially important confounders related to the year during which the patients were diagnosed, the researchers used a propensity-score matching statistical technique, which allowed them to balance historical cohorts of men who had mPCa with contemporary cohorts of such patients.
The median age of both cohorts was 70 years, and the majority of men had received no local treatment for their cancer.
In a Kaplan-Meir analysis, cancer-specific mortality (CSM) rates were 32 months among historical control patients, compared with 36 months for their contemporary counterparts (< .0001).
Overall mortality (OM)–free survival rates were shorter for historical control patients, at 26 months, compared with contemporary patients, at 29 months (< .0001).
On multivariate analysis, cancer-specific mortality rates and OM-free survival rates were 12% lower among contemporary patients compared with historical control patients (hazard ratio [HR] for both endpoints, 0.88; < .0001).
"To the best of our knowledge, this is the first population-based study that demonstrated improvement in CSM and OM in patients with mPCa since the introduction of several novel agents," the researchers write.
"Our results...provide a valid evidence in support of novel agents," they add.

Five New Drugs in Past Decade

The researchers point out that five new drugs have been approved for the treatment of castrate-resistant prostate cancer during the past decade.
These drugs are docetaxel (multiple brands), approved in 2004; cabazitaxel (Jevtana, Sanofi-Aventis), approved in 2010; sipuleucel-T (Provenge, Dendreon Corp), also approved in 2010; abiraterone (Zytiga, Janssen), approved in 2011; and enzalutamide (Xtandi, Astellas), approved in 2012.
Although the magnitude of the difference in both study endpoints between historical and contemporary cohorts was modest, "in terms of absolute net benefit, we showed 4 months [of benefit] in CSM and 3 [months of benefit] for overall survival [in favor of the contemporary cohort], which is absolutely comparable to the survival advantages showed in the original published trials [for these drugs]," Dr Bandini observed.
He added that, unfortunately, the analysis included only men with metastatic disease, for whom the prognosis is poor regardless of the treatment.
Asked by Medscape Medical News to comment on the new findings, Marc Garnick, MD, clinical professor of medicine, Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, Massachusetts, said that the study provides important evidence that men with advanced prostate cancer are living longer compared with similar patients who were treated years ago.
"Those who have been practicing for the past 2 decades can appreciate this study's findings that provide quantification for unmistakable observations that men [with advanced prostate cancer] are living long ― sometimes for years," Dr Garnick said in an email.
"[T]he contribution to improved longevity that has accompanied several of the newer anti–prostate cancer therapeutics has been considerable," he added.
The study did not receive any funding. Dr Bandini has disclosed no relevant financial relationships. Dr Garnick is editor-in-chief of Harvard Medical School's Annual Report on Prostate Diseases and its website.
Int Urol Nephrol. Published online November 11, 2017. Abstract

SUTENT-FIRST FDA APPROVED ADJUVANT TREATMENT FOR HIGH RISK RENLA CANCER

Today, the U.S. Food and Drug Administration (FDA) approved sunitinib malate (Sutent) for the adjuvant treatment of adult patients who are at a high risk of recurrent renal cell carcinoma after nephrectomy.
“This is the first adjuvant treatment approved for patients with renal cell carcinoma, which is significant because patients with this disease who have a nephrectomy are often at high risk of the cancer returning,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “There is now an approved therapy for patients who previously did not have options to potentially reduce cancer recurrence.”
S-TRAC Trial Details
The approval of sunitinib for the adjuvant treatment of renal cell carcinoma was based on the randomized phase III S-TRAC trial of 615 patients with high risk of recurrent renal cell carcinoma following nephrectomy. The study measured disease-free survival.
After 5 years, 59.3% of patients treated with sunitinib had not experienced cancer recurrence or death, compared with 51.3% of patients receiving placebo.
Common side effects of sunitinib include fatigue, diarrhea, mucositis/stomatitis, nausea, decreased appetite/anorexia, vomiting, abdominal pain, hand-foot syndrome, hypertension, bleeding events, dysgeusia, dyspepsia, and thrombocytopenia.
Severe side effects of sunitinib include hepatotoxicity; low left-ventricular ejection fraction; myocardial ischemia/infarction; prolonged QT intervals/Torsade de Pointes; hypertension; hemorrhagic events; tumorlysis syndrome; thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome; proteinuria; thyroid dysfunction; hypoglycemia; osteonecrosis; and wound healing complications.
Patients should stop taking sunitinib if serious skin reactions occur (necrotizing fasciitis, erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis). Women who are pregnant should not take sunitinib because it may cause harm to a developing fetus.
The labeling for sunitinib contains a boxed warning to alert health-care professionals and patients about the risk of hepatoxicity, which may result in liver failure or death.

IMMUNOTHERAPY FOR CERVICAL CANCER

Pembrolizumab (Keytruda) treatment was active in patients with programmed cell death ligand 1 (PD-L1)–positive advanced cervical cancer enrolled in the phase Ib KEYNOTE-028 trial. The findings were reported by Frenel et al in the Journal of Clinical Oncology.
Study Details
In the advanced cervical cancer cohort, 24 patients received pembrolizumab at 10 mg/kg every 2 weeks for up to 24 months. Response according to the Response Evaluation Criteria in Solid Tumors v1.1 was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. The primary endpoint was overall response rate.
The median age of patients was 42 years (range = 26–62 years); 92% had received prior radiation therapy; and 63% had received at least 2 lines of therapy for advanced disease, including bevacizumab (Avastin) in 42%. PD-L1 positivity was defined as membranous staining ≥ 1%; 18 patients were PD-L1–positive in the tumor only and 6 were PD-L1–positive in the tumor and stroma.
Response Rate
At data cutoff, the median follow-up was 11.0 months (range = 1.3–32.2 months). Partial response was observed in four patients (17%), with an additional three patients (13%) having stable disease. The median time to response was 1.9 months (range = 1.7–8.2 months). The median duration of response was 5.4 months (range = 4.1–7.5 months), with 2 patients having response > 6 months. All four responders had PD-L1 expression on the tumor only. The median progression-free survival was 2 months, with rates of 21% and 4% at 6 and 12 months. Median overall survival was 11 months, with rates of 67% and 40% at 6 and 12 months.
Adverse Events
Treatment-related adverse events of any grade occurred in 75% of patients, with the most common being rash (21%) and pyrexia (17%). Treatment-related grade ≥ 3 adverse events occurred in five patients (21%, all grade 3), with rash occurring in 8%. Treatment-related serious adverse events occurred in four patients (17%), including one case each of rash, colitis, Guillain-Barré syndrome, and pyrexia. Treatment was discontinued due to treatment-related adverse events in two patients (8%), consisting of colitis and Guillain-Barré syndrome. Immune-mediated adverse events occurred in six patients (25%), including rash in two, colitis in one, Guillain-Barré syndrome in one, hyperthyroidism in one, and hypothyroidism in one. No treatment-related deaths were observed.
The investigators concluded: “In patients with programmed [cell] death ligand 1–positive advanced cervical cancer, pembrolizumab demonstrated antitumor activity and exhibited a safety profile consistent with that seen in other tumor types.”
The study was funded by Merck & Co., Inc.

TMPRSS2-ERG GENE FUSION PROBABLY PREDICTS A GOOD RISK PROSTATE CANCER

Establishing the way in which a genetic alteration called a TMPRSS2-ERG gene fusion forms in a prostate cancer, rather than the presence of the gene fusion itself, could help identify patients with prostate cancer with a low risk of spreading, which might determine the best course of treatment for the patient. These findings were published by Murphy et al in Cancer Research.
Most prostate cancers are Gleason score 6 (composed entirely of pattern 3), and men with Gleason score 6 are considered at low risk of having their tumors progress.
Senior study author John C. Cheville, MD, Professor of Pathology at the Mayo Clinic in Rochester, Minnesota, explained that active surveillance is a common approach to caring for patients with prostate cancer with a Gleason score of 6. Men on active surveillance receive no treatment and are followed. Some of these men are later found to have clinically significant disease that requires treatment. Identifying a biomarker that, in addition to Gleason score, distinguishes men at increased risk for disease progression from those whose prostate cancer never becomes a clinically significant problem could help improve patient care, added Dr. Cheville.
Study Findings
To look for genetic biomarkers of clinically significant or insignificant disease, Dr. Cheville and colleagues used whole-genome mate pair sequencing to study gene fusions in prostate cancer tissue samples obtained from 133 patients who underwent a radical prostatectomy at the Mayo Clinic. The prostate cancers were divided into four groups: 53 low-volume Gleason 6 tumors were classed as very low risk for progression; 26 high-volume Gleason 6 tumors were classed as low risk for progression; 29 Gleason 7 tumors were classed as intermediate risk for progression; and 25 Gleason 8 or higher tumors were classed as high risk for progression.
The researchers detected TMPRSS2-ERG fusions in 45% of the prostate cancers analyzed, which is consistent with prior studies, according to Dr. Cheville. Fusions were detected in 43%, 49%, 52%, and 24% in the very-low risk, low-risk, intermediate-risk, and high-risk groups, respectively.
Among the 60 prostate cancers with TMPRSS2-ERG fusions, 39 had deleted the interstitial genes between TMPRSS2 and ERG during the fusion event, and 21 had retained these genes. Eighteen of the 21 prostate cancers that had retained the interstitial genes during TMPRSS2-ERG gene fusion were in the very-low risk and low-risk groups.
Information on whether a patient went on to have a biochemical recurrence was available for 34 patients who had prostate cancer with a TMPRSS2-ERG gene fusion with interstitial gene deletion and 22 patients who had prostate cancer with a TMPRSS2-ERG gene fusion with interstitial gene retention. In univariate, but not multivariate, analysis, biochemical recurrence was significantly lower if the prostate cancer had a TMPRSS2-ERG gene fusion with interstitial gene retention compared with those that had interstitial gene deletion.
Commentary
“Our data support results from other studies in that the presence or absence of a TMPRSS2-ERG gene fusion was not predictive of outcome,” Dr. Cheville said. “But how the gene fusion formed was important; the retention of interstitial genes during the fusion event was more common in very-low risk and low-risk cancers, and there may be genes in this region that suppress or limit tumor growth. There is potential utility for determining the status of interstitial genes in stratifying men with prostate cancer into more well-defined risk groups, but this will require further study before it can be incorporated into clinical practice.
“The loss or retention of interstitial genes was tied closely to Gleason score, and we did not have enough cases to determine whether or not the type of fusion was an independent marker for biochemical recurrence,” continued Dr. Cheville. “We need to look at many more samples and also look at patients with higher Gleason scores to determine the extent to which loss of interstitial genes is associated with disease progression.”
According to Dr. Cheville, the main limitation of the study is the relatively small number of patients analyzed in each group.

LOW RATE OF MMR/MSI TESTING PERSISTS

The most recent guidelines recommend that all patients with colorectal cancer (CRC) be tested for deficient DNA mismatch repair (MMR), but until recently, this testing was recommended specifically for two groups of patients ― those at high risk, determined on the basis of personal or family history of CRC, and CRC patients younger than 50 years.
But testing rates have been woefully low, and the latest study shows that the picture remains bleak. Researchers from the Fox Chase Cancer Center, Philadelphia, Pennsylvania, using available data for 152,993 adults with CRC, found that the rate of testing rate was just 28.2%. Only 43.1% of younger patients were tested for MMR/microsatellite instability (MSI) status.
Suboptimal testing rates were reported at academic centers, cancer networks, and across all regions in the United States.
These alarmingly low testing rates are another example of our healthcare system's failure. Dr Nestor Esnaola
"These alarmingly low testing rates are another example of our healthcare system's failure to reliably implement evidence-based best practices and tells us that we are not doing a good job as clinicians, even at cancer networks," corresponding author Nestor F. Esnaola, MD, MPH, MBA, from the Department of Surgical Oncology at the Fox Chase Cancer Center, told Medscape Medical News. "Per guidelines in place when this study was initiated, all younger patients with CRC needed to be tested. It's disappointing that testing rates were as low as 43% in these patients," he added.
These results from the largest study to date were published online November 9 in JAMA Oncology.
"The findings are worrying," writes Stanley R. Hamilton, MD, from the Division of Pathology and Laboratory Medicine at the University of Texas MD Anderson Cancer Center, Houston, writing in an invited commentary.
The study "provides important, national baseline data regarding utilization of MMR deficiency testing in patients with CRC and identifies significant groups at risk for potential nonadherence to newly implemented universal testing guidelines moving forward," write the authors.
Dr Hamilton concurs and notes that the analyses invovled patients with a diagnosis of CRC between 2010 and 2012. "The data are not contemporaneous [testing is currently required for all patients with CRC] but provide a good baseline to determine how testing behavior will change in the future," he told Medscape Medical News.
Dr Hamilton said that he was optimistic that recent approvals of immunotherapy for use in patients with these genetic defects will bring seismic changes in MMR/MSI testing. As reported byMedscape Medical News, earlier this year saw the approval of pembrolizumab (Keytruda, Merck) in May 2017 to treat any tumor associated with a high risk for MSI (MSI-H), and in August 2017, nivolumab (Opdivo, Bristol-Myers Squibb) was approved for use in patients with CRC and MMR/MSI defects.

The Fox Chase Cancer Center Study

For their study, the Fox Chase researchers used the National Cancer Database, which includes data for 70% of all newly diagnosed cases in the United States, to identify patients diagnosed with CRC. The study was conducted from March 2016 to March 2017 ― prior to the approval of any immunotherapy for MSI-H cancer.
The database provided information on MMR/MSI-H testing derived on pathology reports, laboratory reports, admission notes, or consultation notes. "Information was not available as to who ordered the testing," Dr Esnaola told Medscape Medical News.
There were 152,993 patients newly diagnosed with CRC (mean age, 66.9 years; 51% men).
Higher testing rates were seen at academic centers (35.4%), in patients with private insurance (33%), in patients with stage II or III disease (32.7% and 31.5%, respectively), and in patients who underwent examination of 12 or more lymph nodes (33.3%). Testing rates also increased during the 3-year period, from 22.3% in 2010 to 33.1% in 2012 and from 36.1% in 2010 to 48% in 2012 in the younger subset of patients.
"Associations are difficult to explain, such as the higher frequency of testing with larger number of lymph nodes," Dr Hamilton comments. However, Dr Esnaola told Medscape Medical News that the observed association between the number of lymph nodes harvested at colectomy and testing suggests that the association may be a proxy for better cancer care.
Dr Hamilton also noted that some of the associations are actionable. These include the lower frequency of testing in individuals with lower education levels and the underuse of testing associated with older age, residence in a nonmetropolitan county, care at a nonacademic center, and geographic location. "Expanded education of physicians and patients about MSI-H testing could improve adherence to the current guidelines," he writes.
MMR/MSI Testing Should Be Reflexive, Experts Say 
Four gene products are predominantly associated with the MMR system responsible for correction of errors in DNA replication ― MLH1MSH2MSH6, and PMS2. However, methylation in one of the genes, MLH1, results in most of the cases of MMR-deficient CRC. Mutational defects in the germline of any of the four can result in the accumulation of DNA errors when the second copy is inactivated in the tumor, Dr Hamilton pointed out.
He further explained that at MD Anderson, a panel of four antibodies are used in immunohistochemical (IHC) analyses to determine MMR status. A loss in any one of the MMR proteins merits genetic counseling, he said, and the clinician is informed of the results. If an IHC analysis does not detect a loss, polymerase chain reaction assay is conducted for detection of repetitive DNA, if requested.
Knowing MSI status is important in the clinical management of patients with CRC as well as other tumors. "High-level MSI due to somatic MMR gene alterations as well as Lynch syndrome also influences prognosis and therapy decision [in CRC]," Dr Hamilton writes. For example, patients with MSI-H CRC and early-stage disease have a good prognosis. Such patients are likely to live longer with irinotecan-based therapy and are unlikely to respond to fluorouracil-based therapy. In the metastatic setting, patients can be treated with immunotherapies approved to treat MMR/MSI-H tumors.
Dr Hamilton said the increase in testing rates between 2010 and 2012 is a reason for optimism. But Dr Esnaola was more circumspect. "The rates are higher, they but are unacceptably low," he said.
"Although the proportion of patients tested increased during the study period, our results suggest that underutilization of MMR deficiency testing was significant and pervasive, even among young patients with CRC with a well-established risk of Lynch syndrome," Dr Esnaola and colleagues write.

Testing Should Be Routine

Dr Hamilton, a pathologist by training, indicated that testing is ordered across oncology specialties; those who order tests include surgeons, medical oncologists, and treating physicians. At the MD Anderson Cancer Center, pathologists are also involved in determining whether tissue samples are tested even if a test such as MMR/MSI-H is not ordered. "If there is an unbiased recommendation, then a committee votes on allowing a pathologist to do 'reflex' testing," he said. Reflex testing is a test is performed regardless of whether or not it is ordered.
At the Fox Chase Cancer Center, MMR/MSI testing is performed reflexively on all CRC samples, Dr Esnaola said, and he suggested that this is the way forward. "Institutions that aim to optimize colon cancer care should implement reflexive testing," he told Medscape Medical News.
The study identified factors associated with those who are less likely to be tested for MMR/MSI ― increasing age, lower socioeconomic status, being uninsured, and being insured through Medicare. According to the Fox Chase researchers, these data suggest that national guidelines may not be equally implemented across all sociodemographic groups. "This has to change," Dr Esnaola emphasized. "MSI testing should be the standard of care for all CRC patients," he added. With the implementation of reflex testing, the onus is on the hospital to provide MMR testing for all CRC patients, Dr Esnaola noted.
Dr Hamilton told Medscape Medical News that since pembrolizumab was approved to treat all MSI-H tumors, there has been a spike in MMR/MSI testing rates at his institution. He noted that MMR testing is now conducted not only in endometrial, ovarian, and CRC samples but also in pancreatic cancer samples. "Especially in pancreatic cancer, where outcomes are poor, even the approximately 2% of samples that may be MSI-H can benefit from immunotherapy," he said.
Both Dr Esnaola and Dr Hamilton agree that MMR/MSI testing should approach the level of estrogen/progesterone receptor and HER2 testing for breast cancer. "When a woman is diagnosed with breast cancer, these tests are routinely performed," Dr Hamilton noted. It should be the same with MMR/MSI testing for CRC, he said.
Denial of reimbursement for MMR/MSI testing has contributed to the low testing rates, Dr Esnaola and Dr Hamilton indicated. "The guidelines and the FDA approval for these cancers will drive compliance for testing and reimbursement," Dr Hamilton said.
The current endorsement from four societies ― the American Society of Clinical Oncology, the American Society for Clinical Pathology, the Association for Molecular Pathology, and the College of American Pathologists ― of MMR/MSI testing for all CRC patients will help to increase testing. The National Comprehensive Cancer Network and the European Society for Medical Oncology also recommend MMR/MSI testing for all patients with CRC.

STRESS HORMONES MAY PROMOTE RESISTANCE IN EGFR INHIBITORS

Elevated levels of chronic stress hormones, such as those produced by psychological distress, may promote resistance to drugs commonly used to treat lung cancer patients with EGFR mutations, according to new research from The University of Texas MD Anderson Cancer Center. Retrospective analysis of clinical patient data suggests that beta blocker drugs may slow or prevent the development of resistance to EGFR inhibitors.
The research, published by Nilsson et al in Science Translational Medicine, used non–small cell lung cancer (NSCLC) cell lines and mouse models to discover and validate the pathway by which stress hormones drive resistance to these therapies, known as EGFR tyrosine kinase inhibitors.
Approximately 160,000 people in the U.S. are diagnosed with NSCLC each year, and roughly 15,000 have metastatic disease with EGFR mutations, meaning they could benefit from targeted EGFR inhibitors. For these patients, EGFR inhibitors initially work well, but resistance inevitably develops, explained John V. Heymach, MD, PhD, Chair of Thoracic/Head and Neck Medical Oncology at MD Anderson. This resistance is sometimes associated with another EGFRmutation, called T790M, but in other cases the cause is not well understood.
“It is generally accepted that stress is not good for cancer patients, but a cancer diagnosis as well as the necessary treatments can be quite stressful. This data indicates that stress hormones may act directly on tumor cells and promote resistance to therapy,” said Dr. Heymach, the study’s senior author. “The concept that beta blockers, which are well-tolerated and inexpensive, may improve responses to EGFR targeting agents is exciting and should be tested clinically.”
Research Background
Researchers had previously identified a connection between EGFR inhibitor resistance and the immune signaling protein IL-6, which is activated by stress hormones. Therefore, the researchers sought to investigate stress hormone signaling as an alternative mechanism driving resistance to EGFR targeted therapies.
In cultured cell lines, the researchers modeled resistance to common EGFR tyrosine kinase inhibitors, which led to increased levels of IL-6. Stress hormones—such as epinephrine and nor-epinephrine—could increase IL-6 levels by binding to β2-adrenergic receptors and activating specific signaling pathways, explained Monique B. Nilsson, PhD, senior research scientist and the study’s lead author.
“This means that the same type of receptors that sense stress in other parts of your body, like in the lung and blood vessels, are also on tumor cells, and that stress can ‘activate’ these cancer cells as well,” said Dr. Nilsson. “Interestingly, the effect of stress hormones on IL-6 induction was most pronounced in NSCLC cells harboring EGFR activating mutations, and our data indicate there is cooperative signaling between mutant EGFR and β2-adrenergic receptors.”
Preclinical Data and Study Analyses
In mice with transplanted EGFR-mutant tumor cells, chronic stress accelerated tumor growth. Moreover, activation of β2-adrenergic receptors promoted EGFR inhibitor resistance, and this effect could be reversed with beta blockers or IL-6 inhibition.
Based on their preclinical data, the researchers performed retrospective analysis of available patient samples and data from each of the phase III ZEST, BATTLE, and LUX-Lung3 trials.
In patients treated with EGFR inhibitors, higher concentrations of IL-6 in pretreatment plasma samples was associated with significantly worse overall survival than lower IL-6 levels—4.8 months and 11.5 months, respectively. Further, patients using beta blockers had lower levels of plasma IL-6 compared with patients not being treated with beta blockers.
For patients in the LUX-Lung3 study, EGFR inhibitor treatment improved progression-free survival relative to chemotherapy alone, with a median progression-free survival of 11.1 and 6.9 months, respectively. For those patients who happened to be receiving beta blockers during the study, EGFR inhibitors provided an even greater benefit, with a median progression-free survival of 13.6 months compared to just 2.5 on chemotherapy, corresponding to a 75% reduction in the likelihood of progression.
The researchers acknowledge the study was limited in its retrospective analysis of clinical data. While those findings are consistent with data from mouse models and NSCLC cell lines, a prospective randomized study is needed for the highest level of proof and to potentially change the standard of care.
“If beta blockers do truly slow or prevent resistance to EGFR inhibitors, then we may be able to give these patients an oral drug that is well tolerated and only costs a few cents a day—a major benefit for patients and the field,” said Dr. Heymach. 


The researchers are planning prospective studies to investigate the use of beta blockers in treating NSCLC patients with EGFR mutations, and hope to carry out these studies in the next few years.

ABEMACICLIB APPROVED FOR BREAST CANCER

Today, the U.S. Food and Drug Administration (FDA) approved a new indication for fulvestrant (Faslodex), expanding the drug's approved use to include combined therapy with abemaciclib (Verzenio), a cyclin-dependent kinase (CDK) 4/6 inhibitor, for the treatment of hormone receptor–positive, HER2-negative advanced or metastatic breast cancer in women with disease progression after endocrine therapy. Fulvestrant was also approved today by the European Commission (EC) for use in combination with another CDK4/6 inhibitor—palbociclib (Ibrance)—for hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer in women who have received prior endocrine therapy.
About MONARCH 2
The FDA approval is based on data from the phase III MONARCH 2 trial, which met the study’s primary endpoint of progression-free survival. The trial included 669 women with hormone receptor–positive, HER2-negative advanced breast cancer whose disease progressed on or after neoadjuvant or adjuvant endocrine therapy, within 12 months from the end of adjuvant endocrine therapy, or while receiving first-line endocrine therapy for metastatic disease.  
Participants were randomly assigned to receive intramuscular injection of fulvestrant at 500 mg with abemaciclib or placebo orally twice daily in a 2:1 ratio. Pre/perimenopausal women were enrolled in the study and received the gonadotropin-releasing hormone agonist goserelin acetate (Zoladex) for at least 4 weeks prior to and for the duration of the study. Patients remained on treatment until the development of progressive disease or unmanageable toxicity.
Patients enrolled in this study had a median age of 60 years (range = 32–91). The majority of patients in the study were white (56%). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Approximately 59% of patients in each of the treatment arms—fulvestrant in combination with abemaciclib and fulvestrant with placebo—received endocrine therapy as their first therapy for advanced breast cancer; the remaining 38% of patients in the experimental and control treatment arms received this regimen as their second endocrine therapy for advanced breast cancer. Overall, 55.8% had visceral disease and 26.9% had bone-only disease; 25% of patients had primary endocrine resistance, and 2.7% had locally advanced disease.
The results showed a statistically significant increase in investigator-assessed median progression-free survival of 7.1 months (16.4 vs 9.3 months) in patients who received fulvestrant at 500 mg and abemaciclib at 150 mg over fulvestrant and placebo (hazard ratio [HR] = 0.553, 95% confidence interval [CI] = 0.449­­–0.681; P < .0001).
Detailed results of the MONARCH 2 trial were published by Sledge et al in the Journal of Clinical Oncology.

HYPER-PROGRESSION-A NOT SO RARE "ADVERSE EVENT" OF IMMUNOTHERAPY

With all the excitement over the improved survival seen in some patients with cancer treated with immunotherapy, little attention has been paid to the other side of the coin: the fact that some patients get worse.
This phenomenon, referred to as hyperprogressive disease, was highlighted recently in a presentation here at the 18th World Conference on Lung Cancer (WCLC).
Hyperprogressive disease describes an acceleration in tumor growth, as measured on computed tomography, wherein the tumor grows at a faster rate during treatment than the rate at which it was growing before treatment started.
It has previously been described with immunotherapy (reported in 9% of patients with advanced cancer), but until now there have been no data on this phenomenon in patients with lung cancer.  
At the meeting, researchers from the Institut Gustave Roussy, Villejuif, France, led by Roberto Ferrara, MD, presented data from a retrospective analysis of patients they had treated with advanced non-small cell lung cancer (NSCLC). 
They looked specifically for hyperprogressive disease and found it occurred in 14% of patients with advanced NSCLC receiving immunotherapy (single-agent programed cell death inhibitors) and in 5% of patients receiving single-agent chemotherapy.
The figures come from two different sets of patients. From the retrospective analysis of patients with advanced NSCLC who had received immunotherapy at eight different institutions over a period of 5 years (2012 to 2017), the researchers collected data on 333 evaluable patients, with a median follow-up of 12 months.  
Among these patients, 19% had a complete response or partial response to immunotherapy, 39% had stable disease, 42% had progressive disease, 5% had pseudo-progressive disease, and 14% had hyperprogressive disease.
In this subgroup of 56 patients with hyperprogressive disease, tumor growth was accelerated while they were receiving immunotherapy, Dr Ferrara said at the meeting.
This hyperprogressive disease was also associated with pluri-metastatic disease and appearance of new lung lesions, the researchers note.
These patients also had a worse survival than the overall patient population; the median overall survival (OS) was 13 months in the total population but only 3.4 months in the subgroup of patients with hyperprogressive disease. This was even worse than in the subgroup of patients who had progressive disease, for whom the median OS was 5.4 months, which was "as expected" for this group, Dr Ferrara commented.   
The researchers then looked at another group of patients with advanced NSCLC who had received single-agent chemotherapy (most of whom received a taxane; a third of these patients were receiving chemotherapy as third-line treatment, Dr Ferrara noted).
This retrospective analysis included 59 patients with a median follow-up of 26 months. It found that 10% of patients had a complete response or partial response to chemotherapy, 31% had stable disease, 59% had progressive disease, 0% had pseudoprogressive disease, and 5% had hyperprogressive disease. 
The median OS in this population was 8 months, but in the subgroup with hyperprogressive disease it was only 4.5 months.  This was not significantly different from the median OS of 3.9 months seen in the subgroup of progressive disease, Dr Ferrara noted.
In conclusion, Dr Ferrara emphasized that patients with hyperprogressive disease have a shorter survival and noted again the median OS of only 3.4 months with immunotherapy in this subgroup.
Approached for comment, H. Jack  West, MD, medical director of the Thoracic Oncology Program at the Swedish Cancer Institute in Seattle, Washington, told Medscape Medical News: "I think this is interesting and adds some actual data in an area in which we've only had clinical observation/anecdotal experience. But I don't think it really changes how we treat patients — just an indication that a subset of patients are actually harmed by immunotherapy. However, there's no reliable way to identify these patients in advance."
Dr West discusses these new data in some detail in a video. He says the French researchers should be congratulated for this study, which characterizes the phenomenon of hyperprogressive disease in patients with lung cancer receiving immunotherapy for the first time.
The findings should give us "a moment of pause," for they show that not all patients benefit from immunotherapy, and in fact "a significant minority may be harmed," Dr West comments.  
Dr Ferrara and colleagues reported no disclosures. Dr West reports serving as a consultant for Genentech/Roche, Merck & Co, and Clovis Oncology
18th World Conference on Lung Cancer (WCLC). Abstract MA 10.11. Presented on October 17, 2017.