Osimertinib versus afatinib in patients with T790M-positive, non-small-cell lung cancer and multiple central nervous system metastases after failure of initial EGFR-TKI treatment

Background The purpose of this study was to compare the efficacy of osimertinib (OSI) versus afatinib (AFA) in patients with T790M-positive, non-small-cell lung cancer (NSCLC) and multiple central nervous system (CNS) metastases after failure of initial epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. Methods The cohort consisting of 124 patients (OSI: n=60, median age=64.24 years [range, 51.91 to 76.57]; AFA: n=64, median age=64.13 years [range, 50.41 to 77.85]) with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment were consecutively identified at the Cancer Medical Center, Sun Yat-Sen University between March 2017 and July 2017; patients underwent either oral OSI (80 mg/day) or oral AFA (40 mg/day) until the occurrence of disease progression, intolerable adverse events (AEs), or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS). Results After a median follow-up of 24 months (range, 6 to 26), a significant improvement in OS was observed in the OSI group compared with the AFA group (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.23 - 0.41; p = 0.009; median, 13.0 versus 9.2 months). The median duration of PFS was significantly longer with OSI than with AFA (HR 0.25, 95% CI 0.11 - 0.34; p = 0.001; median, 5.4 versus 4.3 months). The proportion of grade 3 or higher AEs was lower with OSI (22.4%) than with AFA (39.4%). Conclusion In patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment, OSI was associated with significantly improved survival benefit compared with AFA, and OSI exhibited a controllable tolerability profile.