Abstract 4623: The relationship of KRAS mutation and clinical outcomes in patients treated with consolidation durvalumab for locally advanced non-small cell lung cancer

Introduction: KRAS G12C is associated with a favorable response to immunotherapy in patients with advanced non-small cell lung cancer (NSCLC), while other KRAS variants show mixed effects. In addition, there is little known on how KRAS mutations affect immunotherapy responsiveness in the curative setting. This study aims to evaluate the impact of KRAS mutations on clinical outcomes of patients treated with consolidation durvalumab for unresected locally advanced NSCLC. Methods: Clinical data were gathered from the medical records of patients seen at The Ottawa Hospital Cancer Centre from June 1, 2019 to Mar 1, 2024. Adult patients with non-squamous NSCLC who completed chemoradiation therapy and received at least 1 dose of consolidation durvalumab were included. Patients were grouped by KRAS mutation as follows, (1) G12C, (2) non-G12C, or (3) wild type/unknown. Real world progression free survival (PFS) was the primary outcome. Univariable analysis was performed using the Cox Proportional Hazards Model. Results: 78 patients were included. The median age was 68 years old and 64% of patients were female. PDL1 expression was <1% in 14 (18%) patients, ≥1% in 51 (65%), and missing in 13 (17%). 50 cases were tested for KRAS and 31 (62%) harbored a KRAS mutation. Of those, 16 (32%) were G12C and 15 (30%) were non-G12C. Non-G12C point mutations included G12V (n=6), G12A (n=3), G12D (n=3), G13D (n=2), and G13V (n=1). The median PFS of the entire cohort was 40.6 months (95% CI: 23.1-58.2), G12C mutated was 32.1 months (95% CI: 26.0-38.1), and non-G12C was 20.5 months (95% CI: 12.7-28.3). Compared to KRAS wild type/unknown, there was a trend to improved PFS in patients with G12C mutations (hazards ratio (HR) 0.48, p=0.17), and shortened PFS in patients with non-G12C (HR 1.47, p=0.35). Furthermore, PDL1≥1% was associated with improved PFS (HR 0.21, p<0.01). Conclusions: This study demonstrates the potential prognostic value of both KRAS G12C and non-G12C mutations in locally advanced unresectable NSCLC treated with consolidation durvalumab. It also supports PDL1 expression as an established biomarker of immunotherapy sensitivity in the real world. Further studies to prospectively validate KRAS as a predictive marker are warranted. Citation Format: William J. Phillips, Michelle Pradier, David J. Stewart, Sara Moore. The relationship of KRAS mutation and clinical outcomes in patients treated with consolidation durvalumab for locally advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4623.