Sorafenib combined with carboplatin/paclitaxel for advanced non-small cell lung cancer: A phase I subset analysis

7194 Background: The EGFR is often overexpressed in advanced non-small-cell lung cancer (NSCLC) - a solid tumor associated with a poor prognosis. Oncogenic k-ras mutations and raised serum VEGF predict poor outcome in NSCLC. In vitro targets of sorafenib include Raf, which is downstream of EGFR and k-ras. Sorafenib also targets the VEGFR-2/-3 tyrosine kinases, involved in tumor angiogenesis. Preclinically, sorafenib targets the tumor and tumor endothelium to inhibit tumor growth. Methods: This subanalysis of a Phase I trial with a Phase II expansion in NSCLC was performed to evaluate the safety (adverse events graded by NCI-CTC 2.0) and preliminary anti-tumor activity (response by RECIST, PFS, TTP) of oral sorafenib combined with carboplatin/paclitaxel in 15 patients with advanced, progressive NSCLC. Carboplatin (AUC 6)/paclitaxel (225 mg/m2) was administered on Day 1, and sorafenib (100, 200, or 400 mg bid) on Days 2–18 of each 21-day treatment cycle. Results: Drug-related adverse events were reported by 73% (11/15) of patients, but were mostly grade 1–2 (53%) in severity; none was grade 4. The most common drug-related events at any grade were dermatologic (Hand-foot skin reaction [20%]; rash [60%]), and gastrointestinal (diarrhea [20%]; anorexia [13%]). There were no drug-related cardiovascular adverse events. Three patients reported grade 1–2 drug-related bleeding events (epistaxis n = 2; other n = 1). Of the 14 evaluable patients, four (29%) had a confirmed PR as best response, seven (50%) had SD, and three (21%) had PD. Therefore, the disease control rate (objective response plus SD) was 79%. Duration of response was 25 weeks. Median PFS was 34 weeks. Discussion: This sorafenib combination was well tolerated and showed promising preliminary anti-tumor activity in patients with advanced, progressive NSCLC. [Table: see text]