Impact of Immunotherapy on the Survival of Patients With Cancer and Brain Metastases

Background: Immunotherapy has shown excellent efficacy in various cancers. However, there is a lack of knowledge regarding the significant role of immunotherapy in patients with brain metastases (BMs). The objective of this study was to investigate, using the National Cancer Database, the impact of immunotherapy on the overall survival (OS) of patients with BMs who did not receive definitive surgery of the primary tumor. Patients and Methods: Patients diagnosed with the primary cancer of non-small cell lung cancer, small cell lung cancer, other types of lung cancer, breast cancer, melanoma, colorectal cancer, or renal cancer who had BMs at the time of diagnosis were identified from the National Cancer Database. We assessed OS using a Cox proportional hazards model adjusted for age at diagnosis, sex, race, education level, income level, residential area, treatment facility type, insurance status, Charlson-Deyo comorbidity status, year of diagnosis, primary tumor type, and receipt of chemotherapy, radiation therapy (RT), and/or immunotherapy, because these factors were significantly associated with OS in the univariable analysis. Results: Of 94,215 patients who were analyzed, 3,097 (3.29%) received immunotherapy. In the multivariable analysis, immunotherapy was associated with significantly improved OS (hazard ratio [HR], 0.694; 95% CI, 0.664-0.726; P<.0001) compared with no immunotherapy. Treatment using chemotherapy plus immunotherapy was significantly associated with improved OS (HR, 0.643; 95% CI, 0.560-0.738; P<.0001) compared with chemotherapy without immunotherapy. RT plus immunotherapy was also associated with significantly improved OS (HR, 0.389; 95% CI, 0.352-0.429; P<.0001) compared with RT alone. Furthermore, chemoradiation (CRT) plus immunotherapy was associated with significantly improved OS (HR, 0.793; 95% CI, 0.752-0.836; P<.0001) compared with CRT alone. Conclusions: In this comprehensive analysis, the addition of immunotherapy to chemotherapy, RT, and CRT was associated with significantly improved OS in patients with BMs. The study warrants future clinical trials of immunotherapy in patients with BMs, who have historically been excluded from these trials.