First- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors in a large, real-world cohort of patients with non-small cell lung cancer

Background: There are limited comparisons of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in large, real-world cohorts of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Methods: Patients with advanced NSCLC (N=612) with common EGFR mutations receiving first-line gefitinib/erlotinib and afatinib were grouped and propensity-score matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutations were analyzed. Results: The gefitinib/erlotinib and afatinib groups each contained 206 patients after matching. Compared with gefitinib/erlotinib, patients receiving afatinib achieved longer median PFS (16.3 versus 14.2months; log-rank test p=0.020) and had a lower risk of progression [hazard ratio (HR) 0.73 (95% confidence interval (CI), 0.57-0.94); p=0.017]. Median OS (37.3 versus 34.2months; log-rank test p=0.500) and reduction in risk of death [HR 0.89 (95% CI, 0.65-1.23); p=0.476] did not differ significantly between groups. T790M positivity was significantly higher in the gefitinib/erlotinib than afatinib group (70.9% versus 44.6%, p<0.001). Multivariate analysis demonstrated that afatinib was independently associated with lower T790M positivity [odds ratio (OR) 0.27 (95% CI, 0.14-0.53); p<0.001], whereas 12months PFS after EGFR-TKI treatment [OR 3.00 (95% CI, 1.56-5.98); p=0.001] and brain metastasis [OR 2.12 (95% CI, 1.08-4.26); p=0.030] were associated with higher T790M positivity. Sequential third-generation EGFR-TKI treatment was administered to 63 patients, in whom median OS after the second-third-generation and first-third-generation EGFR-TKI sequences were 38.8 and 29.1months, respectively. Conclusion: Compared with gefitinib/erlotinib, afatinib had a higher treatment efficacy and a lower secondary T790M positivity in a large, real-world cohort of Asian patients with EGFR-mutated NSCLC.