Approval Summary: Erlotinib Maintenance Therapy of Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Evaluate the relationship between EGFR mutation status and clinical outcomes reported in this study.Identify patients with NSCLC who may be appropriate candidates for first-line maintenance therapy with erlotinib. This article is available for continuing medical education credit at CME.TheOncologist.com. On April 16, 2010, the U. S. Food and Drug Administration (FDA) approved erlotinib tablets (Tarceva®; OSI Pharmaceuticals, Inc., Melville, NY) for maintenance treatment of patients with stage IIIB/IV non-small cell lung cancer (NSCLC) whose disease had not progressed after four cycles of platinum-based first-line chemotherapy. In total, 889 patients received either erlotinib (150 mg) or placebo once daily. Progression-free survival (PFS), in all patients and in patients with epidermal growth factor receptor (EGFR)+ tumors by immunohistochemistry (IHC), was the primary efficacy endpoint. Overall survival (OS) was a secondary sponsor endpoint but was the primary regulatory endpoint. Median PFS times were 2.8 months and 2.6 months in the erlotinib and placebo arms, respectively (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.62–0.82; p < .001). Median OS times were 12.0 months and 11.0 months, favoring erlotinib (HR, 0.81; 95% CI, 0.70–0.95). The PFS and OS HRs in patients with EGFR+ tumors by IHC were 0.69 (95% CI, 0.58–0.82) and 0.77 (95% CI, 0.64–0.93), respectively. The PFS and OS HRs in patients with EGFR− tumors by IHC were 0.77 (95% CI, 0.51–1.14) and 0.91 (95% CI, 0.59–1.38), respectively. Following disease progression, 57% of placebo-treated patients received additional chemotherapy, compared with 47% of erlotinib-treated patients. Fourteen percent of placebo-treated patients received erlotinib or gefitinib, 31% received docetaxel, and 14% received pemetrexed. In total, 59% of placebo-treated patients who received treatment received FDA approved second-line NSCLC drugs. The most common adverse reactions in patients receiving erlotinib were rash and diarrhea.