July 21, 2011 — Another study has shown the benefit of using an EGRF tyrosine kinase inhibitor in patients with nonsmall-cell lung cancer (NSCLC) with tumors that test positive for EGFR mutations.
This latest study, known as OPTIMAL, was conducted in 165 Chinese patients with EGFR-positive NSCLC, and showed that first-line erlotinib (Tarceva) nearly tripled progression-free survival, compared with chemotherapy (13.1 vs 4.6 months; hazard ratio, 0.16; P < .0001).
The results are published online July 22 in the Lancet Oncology.
This is the third study to show the superiority of erlotinib over chemotherapy in patients with EGFR-positive NSCLC. There are also 3 studies showing similar superiority for the other EGFR inhibitor, gefitinib (Iressa), according to an accompanying editorial by Tetsuya Mitsudomi, MD, from the Aichi Cancer Center Hospital in Nagoya, Japan.
These EGFR inhibitor drugs are "undoubtedly key drugs for patients with EGFR mutations and should be used early in treatment," Dr. Mitsudomi writes.
The accumulating evidence led an expert to declare recently that it could now be considered a "tragedy" not to treat these patients with such a drug. The comment was made by Edward Kim, MD, PhD, assistant professor of medicine and director of clinical operations at the University of Texas M.D. Anderson Cancer Center in Houston, at the recent World Conference on Lung Cancer in Amsterdam, the Netherlands.
This involves obtaining and testing tumor tissue, which can be problematic, but "I don't think that we can accept a status unknown anymore," Dr. Kim said.
Lung cancer experts are pushing for all patients to be tested upfront, so that the mutation status can guide the decision over which treatment to use, and so targeted agents such as EGFR inhibitors can be used as first-line therapy.
However, in his editorial, Dr. Mitsudomi notes that "when test results cannot be obtained in a reasonably short timeframe, first-line chemotherapy and second-line EGFR [tyrosine kinase inhibitors] after progression is a reasonable option if the patient is later shown to be EGFR-mutation positive."
Practice-Changing Results
The OPTIMAL study, led by Caicun Zhou, MD, from Shanghai Pulmonary Hospital, and Yi-Long Wu, MD, from the Guangdong Lung Cancer Institute in Guangzhou, China, compared erlotinib with the doublet combination chemotherapy of gemcitabine plus carboplatin.
Erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR-positive NSCLC and was associated with more favorable tolerability, the researchers report. The results suggest that erlotinib is important as a first-line treatment.
"The results of this study have practice-changing implications and provide justification for widespread implementation of routine EGFR-mutation testing in advanced NSCLC," the study authors conclude.
Progression-Free Survival is "Amazing"
The median progression-free survival of 13.4 months seen with erlotinib in this study is "amazing," notes Dr. Mitsudomi in the editorial.
A similar progression-free survival of 14 months was reported with erlotinib in a Spanish phase 2 study in patients with EGFR mutations (N Engl J Med. 2009;361:958-967). In comparison, the median progression-free survival of 9.7 months seen in the recently reported phase 3 EURTAC study, conducted in Europe, was "disappointing," according to Dr. Mitsudomi, although the progression-free survival was double that seen with chemotherapy, again clearly showing a significant superiority of erlotinib over chemotherapy.
In 2 Japanese studies conducted in patients with EGFR-positive tumors with the other EGFR inhibitor, gefitinib, median progression-free survival was 10.4 months in one study (N Engl J Med. 2010;362;2380-2388) and 9.2 months in the other (Lancet Oncol. 2010;11:121-128), Dr. Mitsudomi noted.
The third study with gefitinib — the IPASS study — showed a median progression-free survival of 9.7 months.
Do Not Underestimate the Power
None of these studies have so far shown a benefit in overall survival, Dr. Mitsudomi notes. "Failure to translate extended [progression-free survival] into increased overall survival is accounted for by the substantial crossover of treatment after progression of the disease," he explains.
"Yet this crossover should not lead to underestimation of the power of the EGFR inhibitors in patients with EGFR mutations," Dr. Mitsudomi writes.
A historic comparison of patients in Japan shows that, after the approval of gefitinib, overall survival of patients diagnosed with EGFR-positive NSCLC is now 27.2 months; previously, overall survival was 10.4 to 13.6 months, which is still the case for patients who do not have EGFR mutations, he notes.
The OPTIMAL study was funded by Roche, manufacturer of erlotinib. Dr. Zhou reports receiving grants Roche, and lecture fees from Roche and Eli Lilly, Dr. Wu reports receiving honoraria from Roche, and lecture fees from Eli Lilly, Pfizer, and AstraZeneca. Dr. Mitsudomi reports having served as a consultant to Pfizer and Boehringer Ingelheim, and receiving lecture fees from Chugai, Eli Lilly, and AstraZeneca.
Lancet Oncol. Published online July 22, 2011.
This latest study, known as OPTIMAL, was conducted in 165 Chinese patients with EGFR-positive NSCLC, and showed that first-line erlotinib (Tarceva) nearly tripled progression-free survival, compared with chemotherapy (13.1 vs 4.6 months; hazard ratio, 0.16; P < .0001).
The results are published online July 22 in the Lancet Oncology.
This is the third study to show the superiority of erlotinib over chemotherapy in patients with EGFR-positive NSCLC. There are also 3 studies showing similar superiority for the other EGFR inhibitor, gefitinib (Iressa), according to an accompanying editorial by Tetsuya Mitsudomi, MD, from the Aichi Cancer Center Hospital in Nagoya, Japan.
These EGFR inhibitor drugs are "undoubtedly key drugs for patients with EGFR mutations and should be used early in treatment," Dr. Mitsudomi writes.
The accumulating evidence led an expert to declare recently that it could now be considered a "tragedy" not to treat these patients with such a drug. The comment was made by Edward Kim, MD, PhD, assistant professor of medicine and director of clinical operations at the University of Texas M.D. Anderson Cancer Center in Houston, at the recent World Conference on Lung Cancer in Amsterdam, the Netherlands.
This involves obtaining and testing tumor tissue, which can be problematic, but "I don't think that we can accept a status unknown anymore," Dr. Kim said.
Lung cancer experts are pushing for all patients to be tested upfront, so that the mutation status can guide the decision over which treatment to use, and so targeted agents such as EGFR inhibitors can be used as first-line therapy.
However, in his editorial, Dr. Mitsudomi notes that "when test results cannot be obtained in a reasonably short timeframe, first-line chemotherapy and second-line EGFR [tyrosine kinase inhibitors] after progression is a reasonable option if the patient is later shown to be EGFR-mutation positive."
Practice-Changing Results
The OPTIMAL study, led by Caicun Zhou, MD, from Shanghai Pulmonary Hospital, and Yi-Long Wu, MD, from the Guangdong Lung Cancer Institute in Guangzhou, China, compared erlotinib with the doublet combination chemotherapy of gemcitabine plus carboplatin.
Erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR-positive NSCLC and was associated with more favorable tolerability, the researchers report. The results suggest that erlotinib is important as a first-line treatment.
"The results of this study have practice-changing implications and provide justification for widespread implementation of routine EGFR-mutation testing in advanced NSCLC," the study authors conclude.
Progression-Free Survival is "Amazing"
The median progression-free survival of 13.4 months seen with erlotinib in this study is "amazing," notes Dr. Mitsudomi in the editorial.
A similar progression-free survival of 14 months was reported with erlotinib in a Spanish phase 2 study in patients with EGFR mutations (N Engl J Med. 2009;361:958-967). In comparison, the median progression-free survival of 9.7 months seen in the recently reported phase 3 EURTAC study, conducted in Europe, was "disappointing," according to Dr. Mitsudomi, although the progression-free survival was double that seen with chemotherapy, again clearly showing a significant superiority of erlotinib over chemotherapy.
In 2 Japanese studies conducted in patients with EGFR-positive tumors with the other EGFR inhibitor, gefitinib, median progression-free survival was 10.4 months in one study (N Engl J Med. 2010;362;2380-2388) and 9.2 months in the other (Lancet Oncol. 2010;11:121-128), Dr. Mitsudomi noted.
The third study with gefitinib — the IPASS study — showed a median progression-free survival of 9.7 months.
Do Not Underestimate the Power
None of these studies have so far shown a benefit in overall survival, Dr. Mitsudomi notes. "Failure to translate extended [progression-free survival] into increased overall survival is accounted for by the substantial crossover of treatment after progression of the disease," he explains.
"Yet this crossover should not lead to underestimation of the power of the EGFR inhibitors in patients with EGFR mutations," Dr. Mitsudomi writes.
A historic comparison of patients in Japan shows that, after the approval of gefitinib, overall survival of patients diagnosed with EGFR-positive NSCLC is now 27.2 months; previously, overall survival was 10.4 to 13.6 months, which is still the case for patients who do not have EGFR mutations, he notes.
The OPTIMAL study was funded by Roche, manufacturer of erlotinib. Dr. Zhou reports receiving grants Roche, and lecture fees from Roche and Eli Lilly, Dr. Wu reports receiving honoraria from Roche, and lecture fees from Eli Lilly, Pfizer, and AstraZeneca. Dr. Mitsudomi reports having served as a consultant to Pfizer and Boehringer Ingelheim, and receiving lecture fees from Chugai, Eli Lilly, and AstraZeneca.
Lancet Oncol. Published online July 22, 2011.
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