| Sumario: | Simple Summary: Brain metastases are a serious complication of non-small cell lung cancer (NSCLC) that often lead to poor survival. Combining immunotherapy with brain radiation could be more effective than either treatment alone, but the optimal timing of this combination is unknown. Using real-world data from older adults who had brain metastases at diagnosis of NSCLC, we compared surival outcomes of the combination therapy that was administered within different timing windows. This population is largely underrepresented in clinical trials. Our findings could help clinicians optimize combination treatment strategies for these patients who are at high risk of poor survival outcomes. Immune checkpoint inhibitors (ICIs) display efficacy in non-small cell lung cancers (NSCLCs) with brain metastases (BMs) and studies suggest potential synergy with cranial radiation (CR). However, population-based evaluations of optimal time between ICI-CR combinations are limited in the US. Using SEER-Medicare database (2010–2019), we analyzed patients aged ≥65 years with NSCLC and BM receiving ICI-CR within 6 months of diagnosis, excluding those receiving targeted therapies. First treatment after diagnosis (ICI or CR) was defined as index treatment; followed by subsequent treatment. Findings were validated using an independent cohort from the TriNetX LIVE™ Platform. Patients were grouped by interval between the end of the index treatment and the start of the subsequent treatment: ≤15 days (n = 117), 16–30 days (n = 42), and >30 days (n = 77). Overall survival (OS) was measured from the start of the subsequent treatment until death, end of insurance coverage, or study end. Kaplan–Meier survival curves and multivariable Cox proportional hazards models estimated differences between groups. Among 236 patients, median OS was 134 days, 92 days, and 209 days, respectively. No significant OS differences were found across intervals. However, a survival benefit emerged approximately 300 days after follow-up when ICI was administered within 15 days of CR. These findings offer insight into treatment sequencing in NSCLC with BM and support further investigation in larger cohorts.
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