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http://www.oncologystat.com/home/news/F ... py_US.html


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CHICAGO (EGMN) - Cetuximab improved overall survival of advanced non-small cell lung cancer by about 1.2 months when added to platinum-based chemotherapy in a large international phase III trial that is expected to change first-line treatment for millions of patients.

"Cetuximab added to a platinum-based chemotherapy sets a new standard for the first-line treatment of patients with non-small cell lung cancer," Dr. Robert Pirker, principal investigator of the FLEX trial, announced June 1 at a plenary session during the annual meeting of the American Society of Clinical Oncology.

As presented by Dr. Pirker of the Medical University of Vienna, the highly anticipated results for 1,125 patients from 30 countries are mostly positive but also enigmatic.

Median overall survival improved from 10.1 months in 568 patients given cisplatin and vinorelbine by themselves to 11.3 months in 557 patients who had cetuximab (Erbitux) added to their regimen (Hazard ratio .871, P = .0441). One-year survival also was better with cetuximab (47% vs. 42%), and the response rate rose from 29.2% to 36.3%.

Progression-free survival stayed flat, however, at 4.8 months for both arms of the study, and a planned subgroup analysis revealed "a remarkable difference" in outcomes of white and Asian patients.

Asian patients lived longer overall, but only white patients seemed to fare better when cetuximab was added to chemotherapy. For 121 Asian patients, median overall survival was 17.6 months with cetuximab and 20.4 months without. The same median was only 9.1 months with chemotherapy alone in 946 white patients, but it rose to 10.5 months with the addition of cetuximab.

Dr. Pirker cautioned against drawing conclusions based on these disparities. The Asian population was much smaller, he noted, and it had better prognostic factors - more adenocarcinoma, more females, more never smokers, and more poststudy use of tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) targeted by cetuximab.

"There is no proof that cetuximab does not work in the Asian population. This is not what the FLEX data show," Dr. Pirker said.

The First-Line in Lung Cancer with Erbitux (FLEX) trial was conducted by Merck KGaA in Darmstadt, Germany. It enrolled a broad range of patients who had not been treated for stage IIIB or stage IV non-small cell lung cancer. Nearly half had adenocarcinoma, about a third had squamous cell carcinoma, and the rest had other subtypes.

All patients received 80 mg/m² of cisplatin on day 1 and 25 mg/m² of vinorelbine on days 1 and 8 in 3-week cycles. Patients in the cetuximab arm also received an initial dose of 400 mg/m² of cetuximab that became 250 mg/m² weekly until disease progression or intolerable toxicity.

Dr. Pirker said skin rash, a common side effect of cetuximab, was the main toxicity and easily managed. Grade 3/4 adverse events were slightly higher in the cetuximab arm: 91% vs. 86% with chemotherapy alone.

The febrile neutropenia rates raised the concern of Dr. Thomas J. Lynch in a discussion of the study at the plenary session. He found the rates - 15% with chemotherapy alone and 22% with the addition of cetuximab - high, and said the latter rate is unacceptable.

Dr. Lynch, chief of hematology/oncology at Massachusetts General Hospital, Boston, did agree, however, that cetuximab should be an option for first-line treatment in combination with platinum-based chemotherapy. Having reviewed 15 trials of new agents in NSCLC, he noted that only cetuximab and bevacizumab (Avastin) have been shown to improve overall survival as first-line agents.

Cetuximab should be used, he said, for squamous cell histology and maintenance, and for patients who are ineligible for bevacizumab. He said he was not ready to use it for patients who are eligible for bevacizumab, however, or as a single-agent or a second- or third-line agent. Based on previous phase II studies, he added, cetuximab can be used with other chemotherapy regimens as well.

Dr. Lynch said that the Southwest Oncology Group is planning a trial of cetuximab and bevacizumab together against bevacizumab alone, both with paclitaxel-carboplatin chemotherapy, in advanced NSCLC. Both new agents work, he said, but cost is an issue.

Applying the FLEX data, he estimated 18 weeks of cetuximab would cost $62,208 at his hospital and $54,000 at a private practice. The cost per year of life gained would range from $540,000 to $622,080, he said.

Use of cetuximab should be restricted to patients whose tumors express cetuximab target EGFR, according to Dr. Lynch. Biomarker analysis, particularly with KRAS and FISH (fluorescence in situ hybridization), could improve patient selection and perhaps make cetuximab more cost-effective, he said.

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(Oncology Stat, Elsevier Global Medical News, June 2, 2008, JS MacNeil)


The information contained in these articles may or may not be in agreement with my own opinions. They are not posted as medical advice of any kind.

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