Patients with brain metastases (BMs) who receive immunotherapy have improved overall survival (OS) regardless of any other treatment they receive, according to investigators.
In a study of 3112 patients with BMs from kidney cancer, non-small-cell lung cancer, breast cancer, colorectal cancer, and melanoma, immunotherapy was significantly associated with a 38% decreased risk of death compared with no immunotherapy after adjusting for multiple variables (P <.001), Saber Amin, MD, PhD, of the University of Nebraska Medical Center in Omaha, Nebraska, and colleagues reported in JAMA Network Open. In addition, radiation therapy (RT) plus immunotherapy was significantly associated with a 41% decreased risk of death compared with RT alone (P =.003).
Immunotherapy improved median OS by 7.5 months regardless of what other treatments patients received, according to the investigators. RT plus immunotherapy significantly improved median OS compared with RT alone: 10.4 vs 10.09 months (P =.006).
The investigators found no association between chemotherapy plus immunotherapy or chemoradiation plus immunotherapy with improved OS.
“What is unique in our study is that we found that immunotherapy was associated with significantly improved survival in patients with BMs who received surgery of the primary site, which has not, to our knowledge, been investigated so far,” Dr Amin and coauthors wrote.
The improved OS in patients who received RT in addition to immunotherapy may be associated with the abscopal effect of RT, according to the investigators. “After a tumor is irradiated,” the authors explained, “injury in the tumor may lead to the release of tumor-associated antigens, which can stimulate a tumor-specific immune response, allowing the immune cells (ie, T-cells) to recognize and attack both the primary tumor and metastatic disease in a sort of autovaccination. Immunotherapy may enhance the optimal effect of the abscopal effect by increasing and improving the immune response to tumor-associated antigens, notably when the removal of the primary tumor minimizes tumor burden.”
The authors said it was thought that immunotherapy was ineffective for BMs because it will not cross the blood-brain barrier “or, when it does, its ability to elicit a robust immune response would be limited.” Preclinical and clinical evidence, however, suggest that monoclonal antibodies are able to penetrate the blood-brain barrier in both primary and metastatic brain cancer “and thus could be an excellent option for the treatment of brain metastasis.”
The investigators identified study patients using the National Cancer Database. Of the 3112 patients, 1436 (46.1%) were men, 2714 (87.8%) were White, 257 (8.3%) were Black, and 123 (4%) belonged to other racial and ethnic groups. Overall, 183 patients (5.9%) received immunotherapy, 318 (10.2%) received chemotherapy alone, 788 (25.3%) received RT alone, 1393 (44.8%) received chemoradiation alone, 22 (6.5%) received chemotherapy plus immunotherapy, 72 (8.4%) received RT plus chemotherapy, and 76 (5.2%) received chemoradiation plus immunotherapy.
Amin S, Baine MJ, Meza JL, Lin C. Association of immunotherapy with survival among patients with brain metastases whose cancer was managed with definitive surgery of the primary tumor. Published online September 9, 2020. JAMA Netw Open. doi:10.1001/jamanetworkopen.2020.15444