Efficacy of Afatinib, Erlotinib, and Gefitinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients with brain metastasis: a network meta-analysis

Background: Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have been the standard first-line therapy in patients with metastatic non-small cell lung cancer (NSCLC). There have been no head to head comparisons among gefitinib, erlotinib, and afatinib for such patients, brain metastasis in EGFR-mutant NSCLC. The best EGFR-TKI for their treatment is not yet known. We aimed to assess the relative efficacy among gefitinib, erlotinib, and afatinib using network meta-analysis. Methods: A systematic literature review with electronic databases was conducted. We included patients with brain metastasis and EGFR positive NSCLC. End-points were objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events. Data were extracted from included studies. We regarded different standard chemotherapy regimens as “chemotherapy” for network comparisons. Results: Eight studies involving 446 patients with brain metastasis and EGFR positive NSCLC were enrolled in the meta-analysis. Rank probability showed that afatinib had potentially better PFS compared with gefitinib and erlotinib (HR (95% CI): 0.76 (0.06-6.82); 1.00 (0.04-26.10) and 2.20 (0.03-170.64) respectively). Gefitinib revealed better OS than erlotinib and afatinib (HR (95% CI): 0.42(0.10-1.70); 1.03 (0.01-76.98) and 1.14(0.14-9.01) respectively). The data of objective response rate and adverse events for analysis were not available. Conclusions: The published data for EGFR mutant NSCLC patients with brain metastasis were limited. Our study indicated potentially better outcomes of afatinib and gefitinib in this population.