Characteristics and outcomes of patients (pts) with metastatic KRAS mutant lung adenocarcinomas: Lung Cancer Mutation Consortium (LCMC) database.

Abstract

9021 Background: To better understand outcome heterogeneity in pts with KRAS mutant lung cancers, we analyzed the largest multi-institutional database of pts with metastatic KRAS mutant lung adenocarcinomas. Methods: We reviewed data of all pts who consented to LCMC between 2009-2015. Pts with known KRAS status were included in analyses. Mutation data along with co-mutations were obtained along with clinical outcomes. We evaluated baseline characteristics and association of KRAS data with overall survival (OS), calculated from date of distant metastasis to death, in a univariate and multivariable analyses. The median follow-up was 2.15 years (95% CI: 2.01-2.27). Results: 1655 (86%) of 1918 pts’ data were analyzed. Comparative characteristics are summarized in the Table. Among 450 (23%) pts with KRAS mutations: 58% female, 93% ever smokers, and median age 65 years. Main KRAS subtypes: G12C 39%, G12D and G12V were 18% each. Never smokers with KRAS mutation were more likely to have G12D subtypes (18%; p < 0.001). Pts with KRAS mutation, the median OS was 1.96 years, with 2-year OS rate of 49%. Co-mutations (1-16) were checked in all KRAS mutant pts. Co-mutations were rare (14 pts; 3%). KRAS co-mutations were associated with improved OS in multivariable analyses (HR 0.35; 95% CI: 0.13-0.97; p = 0.04), but not KRAS main subtypes / codons. Co-mutation STK-11 in particular (17 of 92 pts; 18%) was associated with poor OS in univariate (HR 2.16; 95% CI: 1.03-4.54; p = 0.04) and multivariable analyses (HR 2.31; 95% CI: 1.18-5.50; p = 0.02). Pts with KRAS mutations had a trend towards a shorter survival (median OS 1.96 vs. 2.22 years; p = 0.08) and a decreased 2-year OS when compared to KRAS wildtype [49% (95% CI: 44-54%) vs. 55% (95% CI: 52-58%)], respectively. Conclusions: KRAS mutation is a significant predictor of worse survival outcomes in pts with metastatic lung adenocarcinomas. The presence of STK-11 co-mutation was associated with especially poor OS. [Table: see text]