PurposeThe objective of this study was to evaluate the safety and efficacy of immune checkpoint inhibitors in small cell lung cancer patients with brain metastases.MethodsWe retrospectively reviewed the records of small cell lung cancer patients with brain metastases treated with chemotherapy and radiotherapy for brain metastases with or without immune checkpoint inhibitors at our institution from January 2019 to January 2021. Patients were divided into two groups. In Group A, patients received chemotherapy and radiotherapy for brain metastases. In Group B, patients received chemotherapy, radiotherapy for brain metastases and at least four cycles of immunotherapy. Overall survival and intracranial progression-free survival were assessed using Kaplan–Meier estimates and Cox regression models.ResultsA total of 282 patients were enrolled in our study. At the end of the study (May 12, 2021), the median overall survival was 13.3 months among 218 patients in Group A and 33.4 months among 64 patients in Group B (hazards ratio [HR] 0.320, 95% confidence interval [CI], 0.189–0.545, P < 0.001). Both univariate and multivariate analyses suggested that two factors were significantly correlated with overall survival: the inclusion of immunotherapy in the regimen and the presence of extracranial metastases. The median intracranial progression-free survival was 6.93 months in Group A and 10.73 months in Group B (HR = 0.540, 95% CI, 0.346–0.841, P = 0.006). The intracranial objective response rate of Group B was greater than that of Group A, but the intracranial disease control rate was similar between the groups.ConclusionImmunotherapy plus chemotherapy and radiotherapy for brain metastases showed promising efficacy for small cell lung cancer patients with brain metastases.