Prognostic impact of first treatment choice in EGFR mutant non-small cell lung cancer (mNSCLC) patients (pts) per mutation type; retrospective analysis.

Abstract

e19120 Background: mNSCLC pts benefit from EGFR tyrosine kinase inhibitors (TKIs) but also from chemotherapy; the optimal sequencing of these treatments in not known. Methods: mNSCLC pts that received systemic treatment for stage 4 disease were eligible. De-identified data was retrieved from medical records of 6 cancer departments. Overall survival (OS) from diagnosis of metastatic disease was the primary outcome. Multivariate analyses included first line of treatment for metastatic disease (chemotherapy vs. TKI), EGFR mutation type, age, sex, stage at diagnosis, histologic subtype, smoking and performance status (PS). Based on our pilot study, to demonstrate OS HR ≥ 2.0 between pts treated with chemotherapy vs. TKI as first treatment, with significance level of 5% and power of 90%, we needed at least 88 events. Results: 287 pts were eligible, median age 66 years, 38% male, 76% stage 4 at diagnosis, 89% adenocarcinoma, 37% ever smokers, 79% PS 0-1. TKI was first treatment in 83%. Only stage at diagnosis (HR 3.15; 95% C.I. 2.02-4.92) and PS (HR 2.0; 95% C.I. 1.16-3.44) were prognostic. Median OS (mOS) was 26.8 months (95% C.I. 24.1-29.5). Among patients with exon 19 deletion, OS trended to be longer for pts that started chemotherapy first (HR 0.50; 95% C.I. 0.24-1.019, p = 0.056). For patients with L858R, the opposite trend was seen (HR 2.24; 95% C.I. 0.89-5.67, p = 0.088). Interaction of first treatment and mutation type was not significant. Patients ≥ 72 y were unlikely to receive chemotherapy first (p = 0.009). Conclusions: Type of EGFR mutation was neither prognostic nor predictive for OS in this cohort, but may influence the most effective treatment sequence. Further studies are required. All patients TKI first Chemotherapy first N (%) mOS (months, 95% C.I.) N mOS (months, 95% C.I.) N mOS (months, 95% C.I.) All pts 287 (100) 26.8 (24.4-29.2) 237 26.6 (23.2-29.9) 50 37.1 (14.9-59.3) Deletion 19 157 (55) 27.0 (25.4-28.5) 136 27.0 (23.7-30.2) 21 37.1 (7.7-66.5) L858R 67 (23) 24.3 (17.8-30.7) 57 26.7 (20.7-32.7) 10 19.5 (8.1-30.9) Other 10 (3.5) 14.7 (0-39.9) 8 25.6 (4.5-46.7) 2 2.56 (-_) Unknown 53 (18.5) 27.2 (14.6-39.8) 36 17.6 (9.7-25.6) 17 47.8 (21.4-74.2)