Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR Positive Advanced Non-Small Cell Lung Cancer: Updated Analysis of the RESET Study.

Abstract

To report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage EGFR+ non-small-cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group). In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes. The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% CI:14.0-16.1) and 11.9 months (95% CI:8.9-14.6), respectively. The median OS in the osimertinib group was 54.3 months (95%CI:46.7-61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median 59.1, 95% CI:48.7-69.5). This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.