Abstract 6637: Real world outcomes for patients with KRAS G12D -mutated non-small cell lung cancer: A University of California Health Data Warehouse retrospective analysis.

Abstract Background: KRAS is the most common driver mutation in non-small cell lung cancer (NSCLC), with G12C and G12D among its most frequent point mutations. Patients with KRAS G12D mutations are more likely to be never-smokers with worse response to immune checkpoint inhibitors (ICI) compared to those with KRAS G12C. As KRAS G12D-targeted therapies are under development, a greater understanding of real-world outcomes associated with current standard-of-care treatments is warranted. Methods: We retrospectively analyzed NSCLC patients with and without KRAS mutations in the University of California Health Data Warehouse. Time on treatment (ToT) of first-line ICIs was estimated, and ICI-related overall survival (OS) was defined as the time from the first ICI infusion until death or loss to follow up. Kaplan-Meier analysis, Cox proportional hazards model, and student’s t-test were applied. Results: We identified 3,391 NSCLC patients, including 158 patients (5%) with KRAS G12D, and 735 (22%) with other KRAS mutations. Patients had a median (range) age of 64 (20-89) upon diagnosis and 57% were female (Table). Among 842 patient (25%) who received ICIs, 58% were treated with pembrolizumab, 20% with nivolumab (including 5% with ipilimumab), and 8% with either atezolizumab or durvalumab. Compared to patients with other KRAS mutations, there were more Hispanic patients with KRAS G12D (20 versus 36 patients, p 0.01). When adjusting for age, race, and ethnicity in a Cox model, patients with KRAS G12D had similar ToT of ICIs (4.3 versus 4.8 months; p = 0.25; HR, 95%CI: 1.30, 0.83-2.04) and ICI-related OS (9.4 versus 14.0 months; p = 0.36; HR, 95%CI: 1.23, 0.79 - 1.92) as those with other KRAS mutations. Conclusion: Harnessing the power of a structured, multicenter data collective, we describe real-world outcomes from patients with KRAS G12D-mutated NSCLC. Citation Format: Jingtong Liang, Tali Azenkot, Sandip Patel. Real world outcomes for patients with KRAS G12D-mutated non-small cell lung cancer: A University of California Health Data Warehouse retrospective analysis abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6637.