• Benjamin Haaland, Pui San Tan, Gilberto de Castro, and Gilberto Lopes.
• *Centre for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore; †Department of Statistics and Applied Probability, National University of Singapore, Singapore; ‡Health Services and Systems Research, Duke-NUS Graduate Medical School, Singapore; §Clinical Oncology, Instituto do Cancer do Estado de São Paulo, São Paulo, Brazil; ‖Hospital do Coração Cancer Center (HCor Onco), São Paulo, Brazil; and ¶Johns Hopkins University, Baltimore, Maryland.
• J Thorac Oncol. 2014 Jun 1;9(6):805-11.

IntroductionTyrosine kinase inhibitors gefitinib, erlotinib, and afatinib have been compared with chemotherapy as first-line therapies for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor-activating mutations. This meta-analysis compares gefitinib, erlotinib, afatinib, and chemotherapy.MethodsLiterature search was performed using relevant keywords. Direct and indirect meta-estimates were generated using log-linear mixed-effects models, with random effects for study. Study-to-study heterogeneity was summarized using I statistics and predictive intervals (PIs).ResultsLiterature search yielded eight randomized phase 3 clinical trials comparing gefitinib, erlotinib, or afatinib with chemotherapy as first-line therapy in patients with advanced non-small-cell lung cancer during the last 5 years. Hazard ratio meta-estimates for progression-free survival were for gefitinib versus chemotherapy 0.44 (95% confidence interval [CI] 0.31-0.63; 95% PI, 0.22-0.88), erlotinib versus chemotherapy 0.25 (95% CI, 0.15-0.42; 95% PI, 0.11-0.55), afatinib versus chemotherapy 0.44 (95% CI, 0.26-0.75; 95% PI, 0.20-0.98), erlotinib versus gefitinib 0.57 (95% CI, 0.30-1.08; 95% PI, 0.24-1.36), afatinib versus gefitinib 1.01 (95% CI, 0.53-1.92; 95% PI, 0.41-2.42), and erlotinib versus afatinib 0.56 (95% CI, 0.27-1.18; 95% PI, 0.22-1.46). Results for overall response rate and disease control rate were similar. There was no evidence that gefitinib, erlotinib, or afatinib improved overall survival compared with chemotherapy.ConclusionGefitinib, erlotinib, and afatinib out-performed chemotherapy in terms of progression-free survival, overall response rate, and disease control rate. Differences among gefitinib, erlotinib, and afatinib were not statistically significant.

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