Although a modest response to cetuximab-containing regimens was observed in this study, a complete response was lacking. Adding to the lack of adequate efficacy, there were more drug-related AEs and serious AEs observed in cetuximab-containing regimens, with differences mainly attributable to skin toxicities, GI (diarrhea/stomatitis), and hypomagnesemia. These findings led the investigators to conclude that addition of cetuximab to pemetrexed would not improve efficacy in this patient population.
Finally, a randomized phase 3 trial is currently being conducted to study the effects of radiotherapy combined with chemotherapy, with or without cetuximab, in treating patients with stage III nonresectable NSCLC.10 With a multi-arm design, patients were randomized to 1 of 4 arms. In Arm 1, patients will receive a standard dose of radiotherapy (5 days/week, 6 weeks). Concurrent chemotherapy comprising paclitaxel-carboplatin will be administered on days 1, 8, 15, 22, 29, and 36; paclitaxel-carboplatin will also be administered as consolidated chemotherapy. In Arm 2, patients will receive high-dose radiotherapy (5 days/week, 7.5 weeks) as well as concurrent and consolidation chemotherapy, as in Arm 1, on days 1, 8, 15, 22, 29, 36 and 43. In Arm 3, as in Arm 1, patients will receive standard-dose radiotherapy. However, in Arm 3, the patients will also receive cetuximab as well as both forms of chemotherapy. This regimen will be administered periodically for up to 16 weeks. Finally, in Arm 4, patients will receive high-dose radiotherapy, as in Arm 2, and receive concurrent cetuximab, concurrent chemotherapy, and consolidation treatment, as in Arm 3. Treatment will be continued until patients reach a primary end point of overall survival and secondary end points of progression-free survival, safety, and more. This trial is scheduled to be completed in 2014.
Discussion and Summary
Several clinical trials on the use of two biologics in the treatment of lung cancer were presented in this article. The trend of results from these studies is the inconsistent benefit or failure of biologics, in combination with chemotherapy, to prolong survival in this patient population.
Guidelines from ASCO recommend that providers use either bevacizumab or cetuximab as maintenance therapy in the treatment of lung cancer, following the completion of platinum-based chemotherapy.11 However, if platinum-based therapy fails, would these biologics be used as a second-line therapy?
The more important question is whether biologics will ever be used as first-line therapy for the treatment of lung cancer. Until clinical improvement is demonstrated, biologics will remain in their current position as second-line treatment of lung cancer.