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

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. Table. Patient Characteristics. KRAS G12D NSCLC patients (n=158) KRAS NON-G12D NSCLC patients (n=735) P value All NSCLC patients (n=3391) Sex Female 95 (60%) 431 (59%) 0.798 1932 (57%) Male 63 (40%) 304 (41%) 1458 (43%) Age at diagnosis Median (range) 67 (24-86) 61 (24-89) 64 (20-89) Ethnicity Hispanic 20 (13%) 36 (5%) <0.001 259 (8%) Non-Hispanic 136 (86%) 665 (90%) 2994 (88%) Unknown 2 (1%) 34 (5%) 138 (4%) Race Asian 100 (63%) 512 (70%) <0.01 1934 (57%) Black/African American 4 (3%) 44 (6%) 144 (4%) White 25 (16%) 95 (13%) 896 (26%) Others 26 (16%) 56 (4%) 325 (10%) Unknown 3 (2%) 28 (7%) 92 (3%) Smoking Never smoker 10 (6%) 36 (5%) 0.2337 342 (10%) Former smoker 8 (5%) 56 (8%) 189 (6%) Regular smoker 1 (1%) 20 (2%) 40 (1%) Unknown 139 (88%) 623 (85%) 2820 (83%) ICI ToT (months) Median 4.3 4.8 0.25 ICI-related OS (months) Median 9.4 14.0 0.36