3085 - Impact of KRAS Mutation Status on Long-Term Oncological Outcomes in Unresectable Stage III NSCLC Treated with Chemoradiation with or without Immunotherapy

05:00pm - 06:00pm PT

Hall F

Screen: 8

POSTER

Presenter(s)

Ritesh Kumar, MD - Rutgers Cancer Institute of New Jersey, New Brunswick, NJ

R. Kumar, C. Shah, A. Shalaby, M. P. Deek, and S. K. Jabbour; Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ

Purpose/Objective(s): Lung cancer is one of the leading causes of cancer-related mortality. Kristen Rat Sarcoma (KRAS) gene expression is considered an oncogenic driver for the pathogenesis and progression of non-small cell lung cancer (NSCLC). This study explores the impact of KRAS expression on disease related outcomes in patients with NSCLC receiving standard chemoradiation (CRT) with or without the addition of immunotherapy (IO).

Materials/Methods: In our retrospective study, 182 patients with locally advanced NSCLC treated between 2009 and 2024 were evaluated. Patients were stratified by their K-RAS mutation status (mutated vs. wild-type (WT). All patients were unresectable and received definitive CRT, and 45% (n=82) patients did receive IO. Survival outcomes were evaluated by Kaplan-Meier analysis, with log-rank test for subgroup analysis.

Results:

The median age was 66 years [IQR 58.7-75]. 51.1% (n=93) patients were females while 72.5% (n=132) were former smokers and 14.8% (n=27) were current smokers. 89.6% (n=163) had ECOG PS 0-1. Adenocarcinoma was the most common histology (n=96; 52.7%) followed by squamous cell carcinoma (n=72; 39.6%) and mixed histology (7.7%; n=14). Stage III disease was present in 163 patients (89.5%), while stage IIB was present in 19 patients (10.5%). 55% (n=100) patients received definitive CRT, while 45% (n=82) patients received CRT-IO. The median duration of follow-up was 30 months.

In the overall cohort, 31.3% (n=57) patients had KRAS wild-type tumors, 12.1% (n=22) patients had KRAS mutated tumors, and 56.6% (n=103) patients had unknown KRAS status. Median PFS was similar in KRAS-mutated vs. KRAS wild-type groups (16 vs. 12 months; p=NS), as was median OS (49 vs. 54 months; p=NS). However, in KRAS-mutated NSCLC, there was a trend toward improved OS with addition of IO compared to without IO (74 vs. 38 months; p=0.19). On multivariate analysis, addition of IO to CRT was a significant prognostic factor for OS (p=0.032) in patients with KRAS mutated tumors.

Conclusion: In KRAS-mutated, unresectable, locally advanced NSCLC, adding IO to CRT improved OS, highlighting the importance of molecular profiling. Further prospective studies are needed to validate the prognostic and therapeutic roles of KRAS and other mutations.