Immune checkpoint inhibitors as subsequent treatment in older adults with non-small cell lung cancer and synchronous brain metastases.

Background: Immune checkpoint inhibitors (ICIs) have become the mainstay treatment for non-small cell lung cancer (NSCLC). However, there is a lack of studies assessing ICIs as subsequent treatment in older adults with NSCLC and brain metastasis (BM). This retrospective cohort study compared the real-world survival of older patients with NSCLC and BM at diagnosis [synchronous BM (SBM)] previously treated with chemotherapy receiving ICI versus chemotherapy as subsequent treatment.

Methods: Patients with NSCLC and SBM ≥65 years previously treated with chemotherapy were identified using the SEER-Medicare database (2010-2019). Patients receiving new chemotherapy and/or Food and Drug Administration (FDA)-approved ICIs as second/third-line treatment were included, excluding those ever-receiving targeted therapies. Each ICI patient was matched to one chemotherapy patient by time to subsequent treatment (within ±30 days) from diagnosis. Overall survival (OS) time was measured from the start of subsequent treatment to death, censored at disenrollment from Medicare Part A/B, enrollment in Part C, or end of study (December 31, 2019), whichever came first. OS curves were estimated and compared using the Kaplan-Meier (KM) method and log-rank test. Hazard ratio (HR) was estimated using a multivariable-adjusted Cox proportional hazards model.

Results: Matched cohorts included 546 patients [273 in each group; median age 71 (range, 65-87) years]. ICI patients were older, more likely non-Hispanic, with squamous cell carcinoma, and liver metastasis compared to chemotherapy. KM estimated better survival in ICI than chemotherapy {median survival: 209 days [95% confidence interval (CI): 160-275] 155 days (95% CI: 135-187); log-rank P<0.001}. ICI was associated with a lower adjusted hazard of death [HR =0.63; 95% CI: 0.52-0.75; P<0.001] compared to subsequent chemotherapy treatment.

Conclusions: In this population-based study of older patients with NSCLC and SBM previously treated with chemotherapy, subsequent treatment with ICI was associated with improved survival compared to chemotherapy.