Prognostic Implication of G12C Mutation in a Real-World -Mutated Stage IV NSCLC Cohort Treated With Immunotherapy in The Netherlands.

Introduction: With the approval of G12C inhibitors as the second line of treatment for G12C-mutated NSCLC, and the expanding research regarding targeting , it is key to understand the prognostic implication of G12C in the current first line of treatment. We compared overall survival (OS) of patients with stage IV G12C-mutated NSCLC to those with a non-G12C mutation in a first-line setting of (chemo)immunotherapy.

Methods: This nationwide population-based study used real-world data from The Netherlands Cancer Registry. We selected patients with stage IV -mutated lung adenocarcinoma diagnosed in 2019 to 2020 who received first-line (chemo-)immunotherapy. Primary outcome was OS.

Results: From 28,120 registered patients with lung cancer, 1185 were selected with a mutation, of which 494 had a G12C mutation. Median OS was 15.5 months (95% confidence interval [CI]: 13.6-18.4) for G12C versus 14.0 months (95% CI:11.2-15.7) for non-G12C ( = 0.67). In multivariable analysis, subtype was not associated with OS (hazard ratio = 0.95, 95% CI: 0.82-1.10). For the subgroup with programmed death-ligand 1 at 0% to 49% who received chemoimmunotherapy, 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 ( = 0.48). For the subgroup with programmed death-ligand 1 more than or equal to 50% who received monoimmunotherapy, the median OS was 22.0 months (95% CI: 18.4-27.3) for G12C and 18.9 months (95% CI: 14.9-25.2) for non-G12C ( = 0.36).

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