Introduction: Sotorasib has emerged as a treatment option for patients with KRAS-mutated non-small cell lung cancer (NSCLC); however, its effect in patients with brain metastases is not well described. We assessed the intracranial response of sotorasib in a retrospective case series of patients with brain metastases (BMs) at a single institution.

Methods: Patients with KRAS-mutated NSCLC with BMs who received sotorasib at Mass General Brigham Hospitals were included. Patients were stratified into three groups: patients with active BM without local therapy within one month of sotorasib initiation (group 1), patients with active BM with local therapy (surgery or radiation) within one month of sotorasib initiation (group 2), and patients with stable BM (group 3). Intracranial progression-free survival (ICPFS) and overall survival (OS) were explored using Kaplan Meier curves that were compared through log-rank test.

Results: Thirty patients were included (five in group 1; seven in group 2; 18 in group 3). Mean age at sotorasib initiation was 60 years. Most (67 %) patients had between one and four BMs at sotorasib initiation. Median ICPFS was three months (95 % CI: 0- 7.7) from start of sotorasib for group 1, two months (0-5.7) for group 2, and 15 months (6.0-24.0) for group 3 (p-value = 0.02). Median OS was four months (1.9-6.1) for group 1, six months (0-13.7) for group 2, and 12 months (3.5-20.5) for group 3 (p-value = 0.13). 57 % of patients experienced intracranial progression, including 44 % of patients who had stable BM at sotorasib initiation.

Conclusion: While sotorasib may have some intracranial activity, a multidisciplinary approach to BM therapy is still warranted, as are future studies with larger patient samples, controls, and extended follow-up.