Phase II Selection Design Trial of Concurrent Chemotherapy and Cetuximab Versus Chemotherapy Followed by Cetuximab in Advanced-Stage Non-Small-Cell Lung Cancer: Southwest Oncology Group Study S0342

Purpose Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation. Patients and Methods Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m(2)) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m(2) loading dose followed by 250 mg/m(2) weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel-carboplatin for four cycles followed by cetuximab. Results Of 242 patients enrolled, 224 were eligible and assessable for response (106 and 118 patients in the concurrent and sequential arms, respectively). With a median follow-up time of 32 months, the median overall survival was 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P = .57); 1-year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35% to 53%), respectively. Response rates and progression-free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm (15% v5% in the sequential arm; P = .036). Conclusion Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen. J Clin Oncol 28: 4747-4754. (C) 2010 by American Society of Clinical Oncology