Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI.

Abstract

Osimertinib is effective in non-small-cell lung cancer (NSCLC) with an acquired epidermal growth factor receptor (EGFR) T790M mutation, the most common resistance mechanism to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). We aimed to evaluate survival outcome of patients with EGFR-mutant NSCLC who have progressed on previous EGFR TKI therapy. Advanced NSCLC patients with EGFR mutation after acquired resistance to first- or second-generation EGFR TKI who received tumor rebiopsy after EGFR TKI failure from 1 January 2012 to 31 December 2017 were reviewed. Patient clinical characteristics, T790M mutation status, and post-progression survival (PPS) were recorded by chart review. We included 240 patients and the percentage of secondary T790M mutations in first time tissue rebiopsy was 52.9%. 38 of the initial T790M-negative patients received second rebiopsies and 14 (36.8%) of these were T790M positive. The duration between first and second rebiopsy tended to be longer in patients who had T790M mutation in the second biopsy (11.5 vs. 6.9months, p = 0.043). After EGFR TKI failure, the median PPS of patients who had the T790M mutation and history of osimertinib use was 42.6months (95% CI 34.6-50.5), compared to 18.0 (95% CI 9.6-26.4) months in T790M-positive patients without a history of osimertinib use, and 18.8 (95% CI 9.3-28.4) months in patients with no T790M mutation (p < 0.0001). Multivariate analysis showed that history of osimertinib use was correlated with improved survival. These data further emphasize that osimertinib should be a standard of care in patients with pretreated EGFR T790M-positive NSCLC.