Sorafenib in platinum-treated patients with extensive stage small cell lung cancer: a Southwest Oncology Group (SWOG 0435) phase II trial.

Introduction: Sorafenib is a multikinase inhibitor affecting pathways involved in tumor progression and angiogenesis. We conducted a phase II trial of sorafenib in platinum-treated patients with extensive stage small cell lung cancer to determine the tumor response rate, toxicity, and overall survival.

Methods: Patients with histologically confirmed, measurable disease, Zubrod performance status 0 to 1, and no more than 1 prior platinum-based treatment were eligible. Patients were stratified by platinum-sensitivity status: sensitive (progression >90 days after platinum) or refractory (progression during or ≤90 days after platinum). Patients were treated with sorafenib 400 mg orally twice a day continuously on a 28-day cycle.

Results: Of 89 patients registered, 82 were evaluable for toxicity assessment, and 83 were evaluable for response. There were four partial responses seen among the 38 patients in the platinum-sensitive stratum, for an estimated response rate of 11% (95% confidence interval: 3-25%), and one partial response among the 45 patients in the platinum-refractory stratum, for an estimated response rate of 2% (95% confidence interval: 0-12%). The median overall survival estimates were 6.7 months (95% confidence interval: 6.1-9.1 months) for the platinum-sensitive stratum and 5.3 months (95% confidence interval: 3.3-7.5 months) in the platinum-refractory stratum. Nineteen patients discontinued treatment because of adverse events or side effects from therapy.

Conclusions: Based on the lack of disease control seen in our trial, further investigation of single-agent sorafenib in the small cell lung cancer population is not recommended. Combination trials of sorafenib and chemotherapy are ongoing.