P09.25 Role of Immune Checkpoint Inhibitors (ICPi) in KRAS-Mutated Non-Small Cell Lung Cancer (NSCLC)

Abstract

Mutations in KRAS are commonly noted in NSCLC in approximately 30% of cases however effective targeted therapy does not exist. Pre-clinical studies noted increased susceptibility to ICPi. Although subgroup analyses from previously published key immunotherapy trials showed favorable trends towards improved survival, more recent data reported discordant results. We retrospectively reviewed all patients (pts) across MedStar Georgetown Cancer Institute and affiliated facilities with stage IV NSCLC who are PDL1 positive and were treated with ICPi over a 5-year period (1/2013-12/2018). Differences in overall survival (OS) among KRAS-mutated and KRAS wild-type were calculated using Kaplan-Meier methods and Wilcoxon rank sum test for comparison. Proogression-free survival (PFS) was a secondary endpoint. Pre-specified subgroup analyses were also reported. We retrospectively reviewed 129 pts with metastatic NSCLC. 40 pts met eligibility criteria for metastatic NSCLC with positive PDL1 expression and available KRAS mutation status. 11/40 pts (27.5%) were confirmed to have KRAS mutation. Median OS among pts with KRAS-mutated versus wild type was 16.5 and 14.1 months respectively, but not statistically significant, p= 1 (Figure 1a). PFS was also not statistically significant between the two groups (Figure 1b). Although a trend towards increased proportion of KRAS mutations in females was noted, this was not statistically different. Similarly, statistically significant differences were not observed when sub-stratified for race and percentage of PDL1 expression as reported in table 1. Among KRAS-mutated pts, survival differences among these subgroups were also not found (Table 1).View Large Image Figure ViewerDownload Hi-res image Download (PPT) We report no significant survival difference between KRAS-mutated versus KRAS wild-type when treated with ICPi in pts with metastatic NSCLC with positive PDL1 expression. The small number of pts in our study is a possible limitation. Larger studies are warranted to highlight conclusive results in this important subgroup of NSCLC pts who lack successful targeted treatment options.