Characteristics and Outcomes of Patients With Metastatic KRAS-Mutant Lung Adenocarcinomas: The Lung Cancer Mutation Consortium Experience

Abstract

Introduction: Mutations in the KRAS gene are the most common driver oncogenes present in lung adenocarcinomas. We analyzed the largest multi-institutional database available containing patients with metastatic KRAS-mutant lung adenocarcinomas.

Methods: The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional collaboration to study the genomic characteristics of lung adenocarcinomas, treat them with genomically directed therapeutic approaches, and assess their outcomes. Since its inception in 2009, the LCMC has enrolled more than 1900 patients and has performed pretreatment, multiplexed, molecular characterization along with collecting clinical data. We evaluated the characteristics of patients with KRAS mutation in the LCMC and the association with overall survival.

Results: Data from 1655 patients with metastatic lung adenocarcinomas were analyzed. Four hundred fifty (27%) patients had a KRAS mutation, 58% were female, 93% were smokers, and there was a median age of 65 years. Main KRAS subtypes were: G12C 39%; and G12D and G12V at 18% each. Among patients with KRAS mutation, G12D had a higher proportion of never-smokers (22%, p < 0.001). Patients with KRAS-mutant tumors had a trend toward shorter median survival compared to all others in the series (1.96 versus 2.22; P = 0.08) and lower 2-year survival rate (49% [95% confidence interval: 44%-54%] and 55% [95% confidence interval: 52%-58%], respectively).

Conclusions: In the LCMC study, 27% of lung adenocarcinomas patients harbored a KRAS mutation and up to one-third of them had another oncogenic driver. Patients with both KRAS and STK11 mutations had a significantly inferior clinical outcome.

Keywords: KRAS mutation; LKB1 mutation; Lung Cancer Molecular Consortium; Lung adenocarcinomas; Precision oncology; STK11 mutation.