Abstract LB-77: A randomized double-blind placebo-controlled phase II trial of sorafenib and erlotinib or erlotinib alone in previously treated advanced non-small cell lung cancer: Correlative analyses

Abstract

Abstract Background: Sorafenib is an oral multikinase inhibitor of angiogenesis and cellular proliferation which has shown preliminary activity in non-small-cell lung cancer (NSCLC). We conducted a multicenter phase II trial of erlotinib +/− sorafenib in 2nd/3rd line NSCLC. Methods: Patients with previously treated stage IIIB/IV NSCLC were eligible (1-2 prior regimens). Additional eligibility criteria included: ECOG performance status 0-2, all NSCLC histologies, measurable disease, adequate organ function, and the absence of major cardiovascular disease. Patients with treated brain metastases and/or on stable anticoagulation were eligible. Patients were stratified according to squamous/non-squamous histology, prior bevacizumab use, and line of therapy and were randomized 2:1 to receive erlotinib 150mg orally once daily and sorafenib 400mg orally twice daily, or erlotinib and placebo. Patients were also consented for biomarker testing for epidermal growth factor receptor (EGFR) mutations, EGFR amplification, and K-ras mutations. The primary endpoint was to assess the efficacy of each arm in terms of objective response rate (ORR) and progression-free survival (PFS). The trial was designed to enroll 168 patients to demonstrate a 40% improvement on an historical 2.2 month PFS (> 80%, 1-sided 0.1). Results: 168 patients were enrolled from February 2008 to February 2009. Baseline characteristics were well-matched between cohorts (median age, 65 years; 3rd line therapy, 39%; prior bevacizumab, 36%; squamous histology, 30%). The ORRs for the sorafenib/erlotinib and erlotinib/placebo cohorts were 8.1% v. 10.9%, respectively (p=.55). However, the disease control rates (ORR + proportion of patients with stable disease) were 54.1% (sorafenib/erlotinib) v. 38.2% (erlotinib/placebo) (p=.06). The median PFS was 3.25 months (sorafenib/erlotinib) v. 1.87 months (erlotinib/placebo) (HR 0.86 [95% CI 0.60, 1.22], p=.20). 72 (44%) patients had material assessable for EGFR mutation analysis. Among the 67 patients who were found to have EGFR wild-type (WT) tumors, the median PFS was 3.25 months (sorafenib/erlotinib) v. 1.71 months (erlotinib/placebo) (HR 0.55 [95% CI 0.32, 0.96], p=.02). Conclusions: Additional preplanned subset analyses based on histology, EGFR amplification, K-ras mutation, prior bevacizumab treatment, and line of therapy will be presented, as well as updated overall response, PFS, survival, and toxicity data. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-77.