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J Thorac Oncol. 2014 Jun;9(6):805-11. doi: 10.1097/JTO.0000000000000156.

Meta-analysis of first-line therapies in advanced non-small-cell lung cancer harboring EGFR-activating mutations.

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*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.



Tyrosine 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.


Literature 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).


Literature 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.


Gefitinib, 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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