Emerging profile of cetuximab in non-small cell lung cancer.

This paper summarizes the phase II and III clinical trial experience with cetuximab in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Single-arm and randomized phase II studies show that adding cetuximab to platinum-based doublets has favorable efficacy compared to chemotherapy alone or historical control groups that did not receive cetuximab. Two phase III studies have been conducted with different primary endpoints: overall survival in the pivotal FLEX trial, and progression-free survival (PFS) as assessed by an independent radiologic review committee in the supportive BMS 099 trial. FLEX shows that adding cetuximab significantly prolongs survival compared to chemotherapy alone. BMS 099 did not meet its primary objective, but did show that adding cetuximab significantly prolongs PFS as assessed by investigators. Across all studies, the safety and tolerability of adding cetuximab was predictable and manageable, and did not exacerbate the toxicity associated with chemotherapy. These trials enrolled a broad population of NSCLC patients regardless of histological subtype or comorbid cardiovascular disease, populations that have been underrepresented in clinical trials of other biologics. Cetuximab does not carry restrictions in use due to safety, and therefore it may be a particularly valuable option for patients who are not eligible for other biologics.