Abstract 4623: The relationship of KRAS mutation and clinical outcomes in patients treated with consolidation durvalumab for locally advanced non-small cell lung cancer
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".