Among treatment modalities for lung cancer, the most promising therapy is the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Both erlotinib and gefitinib, the two first-generation EGFR-TKIs, exhibit significant clinical responses for patients with lung adenocarcinoma. However, few studies have compared the effects of these two drugs, and results have been inconclusive because of the small sample sizes in these studies. Therefore, this study was conducted to investigate this issue. This retrospective nationwide cohort study enrolled NSCLC patients who received EGFR-TKIs after previous chemotherapy in Taiwan between 1996 and 2010 from the National Health Insurance Research Database. Clinical response and survival after receiving erlotinib and gefitinib were compared using logistic and Cox regression analyses, respectively. Inverse propensity score weighting and a sensitivity analysis in the EGFR-TKI responder (clinical improvement by taking EGFR-TKIs for 90 days), adherent patients (receiving EGFR-TKI on a daily basis), adenocarcinoma, and adenocarcinoma with second-line TKIs subgroup were performed for bias adjustment. A total of 7222 patients, including 4592 (63.6%) who received gefitinib, were identified. In the survival analysis, erlotinib was associated with a decline in 1-year progression-free survival (PFS) (hazard ratio, HR: 1.15 [1.09-1.21]) and overall survival (OS) (HR: 1.10 [1.03-1.18]). The effects of various TKIs were consistent in the 4939 EGFR-TKI responders, adherent subgroup, adenocarcinoma subgroup, and adenocarcinoma with second-line TKIs subgroup. In previously treated EGFT-TKI-naive NSCLC patients, those receiving gefitinib exhibited a longer PFS and OS than those receiving erlotinib. Additional large-scale randomized controlled trials are warranted to confirm this finding.
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