P3.01-53 Comparison of the Treatment Efficacy of Osimertinib in Young and Elderly Patients with T790M-Positive NSCLC

Abstract

Osimertinib is a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The AURA3 trial showed that osimertinib is superior to platinum doublet chemotherapy in T790M-positive non-small cell lung cancer (NSCLC) with acquired resistance to first or second generation EGFR-TKIs in patients, irrespective of age. In contrast, another study showed that first or second generation EGFR-TKIs may have poorer efficacy and prognosis in young subjects than in elderly patients with EGFR mutation-positive NSCLC. Thus, we aimed to determine whether osimertinib exerted similar effects on young and old patients with T790M-positive NSCLC. We retrospectively investigated T790M-positive NSCLC patients with acquired resistance to first or second generation EGFR-TKIs who were administered osimertinib therapy from May 2015 to January 2018 by referring to their charts in the Tokyo Metropolitan Cancer and Infectious disease Center, Komagome Hospital, Japan. We defined patients > 65 years old as elderly and those < 65 years old as young. We compared the clinical characters, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the two age groups. Total 31 patients with acquired resistance to first or second generation EGFR-TKIs were administered osimertinib. Twenty-three subjects belonged to the older age group, while 8 belonged to the younger age group. The median ages of the elderly and young patients were 75 years (range: 65–88 years) and 54 years (34–64) years, respectively. There were no significant differences in their clinical characteristics (sex, Eastern Cooperative Oncology Group Performance Status, smoking history, histology, type of de novo EGFR mutation, initial EGFR-TKI therapy, re-biopsy sample, central nervous system metastasis, and osimertinib line). The median PFS duration after initial EGFR-TKI treatment was greater in the elderly patients (17.2 vs. 10.5 months; hazard ratio; 2.86; 95% confidence interval [CI] , 1.03–7.97; P = 0.0022); the ORR of osimertinib in the elderly and young patients was 53.3% and 37.5%, respectively. The median follow up interval after osimertinib initiation was 10.1 months. The total median PFS duration was 5.6 months. The median PFS duration tended to be greater in elderly patients (3.5 vs. 9.1 months; hazard ratio; 1.90; 95% CI, 0.75–4.78; P = 0.17). The median OS duration after osimertinib initiation was significantly greater in elderly patients (5.3 months vs. NA; hazard ratio; 3.36; 95% CI, 1.11–10.1; P = 0.027). Osimertinib showed poorer efficacy in younger patients than in elderly patients with T790M positive NSCLC.