Objectives In patients with Kirsten Rat sarcoma (KRAS) mutated non-small cell lung cancer (NSCLC), the G12C submutation is seen in 40%. With the expanding research regarding KRAS G12C it is key to understand the prognostic implication of KRAS G12C. We compared overall survival (OS) of patients with stage IV KRAS G12C mutated NSCLC to those with a KRAS non-G12C mutation on first line (chemo-)immunotherapy (ICI).

Methods This nationwide population-based study used real-world data from the Netherlands Cancer Registry. We selected patients with stage IV KRAS mutated lungcarcinoma diagnosed in 2019-2020 that received first line (chemo-)ICI. Primary outcome was OS.

Results 1185 patients with a KRAS mutation were selected, 494 had a KRAS G12C mutation (41.7%). Median OS, regardless of treatment type, was 15.5 months (95% CI 13.6-18.4) for KRAS G12C, versus 14.0 months (95% CI 11.2-15.7) for KRAS non-G12C, p=0.67. In multivariable analysis KRAS status was not associated with OS (HR 0.95, 95% CI 0.82-1.10). For the programmed death-ligand 1 (PD-L1) 0-49% subgroup that received chemo-ICI, median OS was 13.3 months (95% CI 10.5-15.2) for G12C, and 9.8 months (95% CI 8.6-11.3) for non-G12C, p=0.48. For the PD-L1 ?50% subgroup receiving mono-ICI median OS was 22.0 months (95% CI 18.4-27.3) for G12C and 18.9 months (95% CI 14.9-25.5) for non-G12C, p=0.36. In the PD-L1 ?50% subgroup there was no difference in OS regarding treatment type (mono-ICI or chemo-ICI) and KRAS mutational status (p=0.32).

Conclusion There was no influence of KRAS subtype (G12C versus non-G12C) on OS in patients with KRAS mutated stage IV NSCLC treated with first-line (chemo-)ICI.