Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation

摘要: BACKGROUND The efficacy of afatinib, an irreversible ErbB Family Blocker, was evaluated in patients who had 1 4 categories solid tumors with epidermal growth factor receptor/human receptor 2 (EGFR/HER2) gene amplification or EGFR-activating mutations. METHODS Patients previously treated but inhibitor-naive esophagogastric, biliary tract, urothelial gynecologic cancers (lung were excluded) harboring EGFR/HER2 high polysomy identified by fluorescence situ hybridization (FISH). Tumors also screened for EGFR mutations. The primary endpoint the objective response rate; secondary endpoints included clinical benefit rate, pharmacokinetics, and safety. RESULTS Of 385 prescreened patients, 38 FISH-positive (10 29 HER2 [1 tumor polysomy]; none mutations), 20 received treatment afatinib 50 mg daily. rate 5% (1 patients), best complete response. Eight experienced stable disease. most frequently reported adverse events diarrhea, rash, decreased appetite. trial closed early because slow recruitment. CONCLUSIONS Single-agent activity limited, yet encouraging, selected that prospectively target activation. implementation a biomarker-driven approach using low-frequency biomarker patient selection across multiple types can be challenging. Cancer 2013;119:3043—3051. © 2013 American Society.