Patients with advanced non-small-cell lung cancer (NSCLC) who received cetuximab (Erbitux) plus chemotherapy lived on average 5 weeks longer than patients who received chemotherapy alone, according to results of a randomized phase III trial reported at the 2008 annual meeting of the American Society of Clinical Oncologists (ASCO). (The results from the study, known as the FLEX trial, were subsequently published in The Lancet on May 2, 2009.)
In the trial, 1,125 patients with advanced NSCLC that tested positive for the epidermal growth factor receptor (EGFR) were randomly assigned to receive standard platinum-based chemotherapy alone or chemotherapy plus cetuximab. Cetuximab is a monoclonal antibody that binds to EGFR and prevents it from stimulating growth of the cell. Nearly all of the patients in the study had stage IV disease. Median overall survival was statistically significantly longer for patients who received cetuximab plus chemotherapy (11.3 months) than for those who received chemotherapy alone (10.1 months).
The benefit of the combination therapy was seen in patients with all histological subtypes of NSCLC, including adenocarcinoma and squamous cell carcinoma, the two most common subtypes. The main side effect was an acne-like skin rash that could be managed. (A subset analysis published December 20, 2010, in Lancet Oncology examined outcomes of patients who experienced this type of rash. The analysis found that those patients who developed a rash during their first treatment cycle were more likely to benefit from treatment than those who experienced the rash later or not at all. Previous studies have found an association between the presence of a rash and response to cetuximab in patients with other cancer types as well.)
"Patients with advanced NSCLC have limited treatment options, and life expectancy is short, so the survival increase shown in this study is an important step for these patients," noted Robert Pirker, M.D., an associate professor of medicine at the Medical University of Vienna in Austria and the study's lead author.
At the time of the ASCO presentation, the only other randomized phase III trial to show a survival benefit in previously untreated advanced NSCLC was a 2005 study of bevacizumab (Avastin) plus chemotherapy. Unlike the current study, that trial did not include patients with squamous cell carcinoma.
Thomas Lynch, M.D., of Massachusetts General Hospital, who commented on the findings at ASCO, said the study was well done and produced "a clinically meaningful benefit for a large population."