Phase III Study of Carboplatin and Paclitaxel Alone or With Sorafenib in Advanced Non Small-Cell Lung Cancer

Purpose This phase If, multicenter, randomized, placebo controlled trial assessed the efficacy and safety of sorafenib, an oral multikinase inhibitor, in combination with carboplatin and paclitaxel in chemotherapy naive patients with unresectable stage IIIB or IV non small-cell lung cancer (NSCLC). Patients and Methods Nine hundred twenty-six patients were randomly assigned to receive up to six 21 day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m(2) (CP) on day 1, followed by either sorafenib 400 mg twice a day (n = 464, arm A) or placebo (n = 462, arm B) on days 2 to 19. The maintenance phase after CP consisted of sorafenib 400 mg or placebo twice a day. The primary end point was overall survival (OS); secondary end points included progression free survival and tumor response. Results Overall demographics were balanced between arms; 223 patients (24%) had squamous cell histology. On the basis of a planned interim analysis, median OS was 10.7 months in arm A and 10.6 months in arm B (hazard ratio [HA] = 1.15; 95% Cl, 0.94 to 1.41; P = .915). The study was terminated after the interim analysis concluded that the study was highly unlikely to meet its primary end point. A prespecified exploratory analysis revealed that patients with squamous cell histology had greater mortality in arm A than in arm B (HR = 1.85; 95% Cl, 1.22 to 2.81). Main grade 3 or 4 sorafenib-related toxcities included rash (8.4%), hand-foot skin reaction (7.8%), and diarrhea (3.5%). Conclusion No clinical benefit was observed from adding sorafenib to CA chemotherapy as first-line treatment for NSCLC.