67P Distinct concomitant genetic alterations in EGFR-mutant non-small cell lung cancer patients with brain metastases

Abstract

EGFR-mutant NSCLC with brain metastases displays diverse trajectories to tyrosine kinase inhibitor (TKI) treatment. Exploring concomitant genetic alterations might describe the underlying mechanisms and identify different subsets of patients. From Jan 2013 to Dec 2020, NSCLC patients with brain metastases were screened and patients harboring EGFR mutation enrolled. Clinical data of patients with next-generation sequencing (NGS) data were then analyzed. Kaplan-Meier method and the Cox proportional hazards model were used for survival analysis. Based on the multivariable analysis, a nomogram was constructed using R version 4.0.5. A total of 2657 NSCLC patients with brain metastases were screened and 737 harboring EGFR mutation, among 73 patients with NGS data, all receiving EGFR TKI treatment, the median age was 58.1years, 35(47.9%) were male, 35(47.9%) were EGFR 19Del. Median overall survival (OS) were 23.6 months. Fifty-five patients (75.3%) harbored concomitant alterations, with TP53 (45.2%), EGFR amplification (12.3%) and RB1(9.6%) being the top three most frequently alterations. Concomitant genetic alterations were significantly associated with reduced OS(23.2 months vs NR, P=0.016). Especially, TP53 mutation (HR=1.8, 95%CI:1.0-3.2) and EGFR amplification (HR=2.5, 95%CI:1.2-5.6) were associated with significantly worse OS. Among the patients with driver genes(HR= 8.0, 95%CI:2.0-31.1) or tumor suppressor genes(HR= 10.6, 95%CI:1.8-60.2) had significantly worse OS than patients without concomitant alterations. However, OS was comparable for patients with local surgical or radiotherapy. As shown in the nomogram, a higher total score was associated with having EGFR 19del mutations and without concomitant alterations indicated a higher likelihood of longer OS. This study reveals the widespread existence of concomitant alterations in patients with EGFR-mutant NSCLC with brain metastases. Concomitant alterations were associated with the poorer clinical outcomes of patients. Based on the nomogram, we identified that the subset of patients without concomitant alterations and EGFR 19Del could derive more survival benefit from the EGFR-TKI treatment.