Survival of patients with KRAS G12C mutated stage IV non-small cell lung cancer with and without brain metastases treated with immune checkpoint inhibitors
Menée aux Pays-Bas à partir de données portant sur 153 patients atteints d'un cancer du poumon non à petites cellules de stade IV présentant la mutation G12C au niveau du gène KRAS, cette étude évalue l'efficacité, du point de vue de la survie globale et de la survie sans progression, d'un traitement de première ligne par inhibiteurs de points de contrôle immunitaire avec ou sans chimiothérapie, en fonction de la présence de métastases cérébrales
Introduction: Few data is available on whether brain metastases (BM) influence survival in patients with stage IV KRAS G12C mutated (KRAS G12C + ) non-small cell lung cancer (NSCLC) treated with first-line immune checkpoint inhibitor (ICI) +/- chemotherapy ([chemo]-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 January 1 – June 30, 2019, treated with first-line (chemo)-ICI. OS and PFS were estimated using Kaplan-Meier methods and BM+ and BM− groups were compared using log-rank tests. Results: Of 2489 patients with stage IV NSCLC, 153 patients had KRAS G12C+ and received first-line (chemo)-ICI. Of those patients, 35% (54/153) underwent brain imaging (CT and/or MRI), of which 85% (46/54) MRI. Half of the patients with brain imaging (56%; 30/54) had BM, concerning one-fifth (20%; 30/153) of all patients, of which 67% was symptomatic. Compared to BM−, patients with BM+ were younger and had more organs affected with metastasis. Around one-third (30%) of patients with BM+ had ≥5 BM at diagnosis. Three quarters of patients with BM+ received cranial radiotherapy prior to start of (chemo)-ICI. The 1-year cumulative incidence of intracranial progression was 33% for patients with known baseline BM and 7% for those without (p = 0.0001). Median PFS was 6.6 (95% CI 3.0–15.9) and 6.7 (95% CI 5.1–8.5) months for BM+ and BM− (p = 0.80), respectively. Median OS was 15.7 (95% CI 6.2–27.3) and 17.8 (95% CI 13.4–22.0) months for BM+ and BM− (p = 0.77), 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 known baseline BM, justifying regular imaging during treatment. In our study, presence of known baseline BM did not influence OS or PFS.
Lung Cancer 2023