Abstract
Abstract INTRODUCTION Sotorasib has emerged as a favorable treatment option for patients with advanced KRAS-mutated non-small cell lung cancer (NSCLC) including those with brain metastases (BM). The objective of this study was to determine the efficacy of sotorasib in the treatment of pre-treated BMs in patients with NSCLC. METHODS This retrospective cohort study included adult patients with KRAS-mutated NSCLC with BMs who received sotorasib between April-2021 and March-2023 at Mass General Brigham Hospitals. Intracranial progression-free survival (ICPFS) and overall survival (OS) were the primary endpoints and were explored using Kaplan Meier analyses for three groups of patients: patients with active BMs and no local therapy (1), patients with active BMs with local treatment within one month of sotorasib initiation (2) and patients with radiographically stable BMs following previous local treatment (3). RESULTS 31 patients with NSCLC and BMs were included (23% male). Mean age at start of sotorasib was 60. 87% of patients had primary lung adenocarcinoma, and 68% of patients had between 1 and 4 BMs when they started sotorasib. Differences in survival distributions for ICPFS for patients in each of the three groups were statistically significant, χ2(2) = 7.600, p = 0.022. Median ICPFS was 3 months (95% CI: 0 – 8.9) from start of sotorasib for group 1, 5 months (0-11.5) group 2, and 15 months (0-33.5) for group 3. Median OS was 4 months (0-8.8) for group 1, 6 months (0-13.7) for group 2, and 12 months (3.6-20.4) for group 3. 55% of patients experienced intracranial progression on sotorasib, including 39% of patients who had stable BMs at sotorasib initiation. CONCLUSION The results of this study indicate that while sotorasib does have intracranial activity, a multimodal approach to BM therapy is still warranted, as are future studies with larger patient samples, controls, and extended follow up.
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