Introduction Few data is available on whether brain metastasis (BM) influences survival in patients with KRAS G12C mutated (KRAS G12C+) stage IV non-small cell lung cancer (NSCLC) treated with first-line (chemo)-immunotherapy (ICI).

Methods Data was retrospectively collected from the population-based Netherlands Cancer Registry. The cumulative incidence of intracranial progression, overall survival (OS) and progression free survival (PFS) was determined for patients with KRAS G12C+ stage IV NSCLC diagnosed between January 1 2019 and June 30 2019, treated with first-line (chemo)-ICI. OS and PFS were estimated using Kaplan-Meier curves, BM+ and BM- groups were compared using log-rank tests.

Results Of 2489 patients with stage IV NSCLC in the registry, 153 patients had KRAS G12C+ non-squamous carcinoma and received (chemo)-ICI in the first line, these were included. One-fifth (n=30) had baseline BM, of which 67% were symptomatic. Of all patients, 35% (54/153) underwent brain imaging, of which 85% (46/54) MRI. Half of the patients with brain imaging (56%; 30/54) had BM. The 1-year cumulative incidence of intracranial progression was 33% for patients with BM and 7% for those without (p=0.0001). Median OS was 15.7 and 17.8 months for BM+ and BM- (p=0.77), respectively. Median PFS was 6.6 and 6.7 months for BM+ and BM- (p=0.80), respectively.  

Conclusion Baseline BM are common in patients with metastatic KRAS G12C+ NSCLC. During (chemo-)ICI treatment, intracranial progression was more frequent in patients with BM, justifying regular imaging during treatment. In our study, presence of baseline BM did not influence OS and PFS.