A Randomized Phase II Study of Gefitinib Plus Simvastatin Versus Gefitinib Alone in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

Purpose: To evaluate the efficacy and safety of gefitinib plus simvastatin (GS) versus gefitinib alone (G) in previously treated patients with advanced non-small cell lung cancer (NSCLC). Experimental Design: Between May 2006 and September 2008, 106 patients (51% men, 75% adenocarcinoma, 50% never smoker) were randomly assigned to G alone (250 mg/d, n = 54) or GS (250 and 40 mg/d, respectively, n = 52). One cycle was 4 weeks of treatment. Therapy was continued until disease progression or intolerable toxicity was observed. The primary endpoint was response rate (RR). Secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). Results: The RR was 38.5% (95% CI, 25.3-51.7) for GS and 31.5% (95% CI, 19.1-43.9) for G. The median PFS was 3.3 months [M] (95% CI, 1.4-5.2M) for GS and 1.9M (95% CI, 1.0-2.8M) for G. The median OS was 13.6M (95% CI, 7.1-20.1M) for GS and 12.0M (95% CI, 7.8-16.2M) for G. In exploratory subgroup analysis, GS showed higher RR (40% vs. 0%, P = 0.043) and longer PFS (3.6M vs. 1.7M, P = 0.027) compared with G alone in patients with wild-type epidermal growth factor receptor (EGFR) nonadenocarcinomas. Adverse events in both arms were generally mild and mainly consisted of skin rashes. Conclusions: Although no superiority of GS to G was demonstrated in this unselected NSCLC population, GS showed higher RR and longer PFS compared with G alone in patients with wild-type EGFR nonadenocarcinomas. Simvastatin may improve the efficacy of gefitinib in that subgroup of gefitinib-resistant NSCLC patients. Clin Cancer Res; 17(6); 1553-60. (C) 2011 AACR.