Adding Immunotherapy to Radiotherapy May Improve OS in Patients with Brain Metastases

A study published in JAMA Network Open found that the addition of immunotherapy to radiotherapy was associated with improved overall survival (OS) compared with radiotherapy alone in patients with brain metastases who received definitive surgery of the primary tumor site.

“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 the tumor burden,” the authors explained. “Radiation therapy also causes the release of neoantigens and upregulation of inflammatory cytokines, which promote the presentation of the neoantigens in the tumor microenvironment and thereby increase the immunogenicity of the tumor cells, making them a better target for immunotherapy.”

This comparative effectiveness study evaluated 3112 adult patients from the National Cancer Database from 2010 to 2016 non-small cell lung cancer, breast cancer, melanoma, colorectal cancer, or kidney cancer and brain metastases at the time of diagnosis and who received definitive surgery of the primary site. The analysis was conducted from March to April 2020.

Of the overall study cohort, 1436 (46.14%) patients were men, 2714 (87.72%) were white, 257 (8.31%) were black, and 123 (3.98%) belonged to other racial and ethnic groups. The median (range) age at diagnosis was 61 (19-90) years of age.

In total, 183 (5.88%) patients received immunotherapy. More specifically, 318 (10.22%) received chemotherapy alone, 788 (25.32%) received radiation alone, 1393 (44.76%) received chemoradiation alone, 22 (6.47%) received chemotherapy plus immunotherapy, 72 (8.37%) received radiotherapy plus immunotherapy, and 76 (5.17%) received chemoradiation plus immunotherapy.

Patients who received immunotherapy were found to have significantly improved OS compared with those who received no immunotherapy in multivariable analysis (HR, 0.62; 95% CI, 0.51-0.76; P < .001). Further, treatment with radiotherapy plus immunotherapy was associated with significantly improved OS compared with radiotherapy alone (HR, 0.59; 95% CI, 0.42-0.84; P = .003). However, chemotherapy plus immunotherapy or chemoradiation plus immunotherapy were not associated with improved OS.

“The improved OS with the addition of immunotherapy to [radiotherapy] may indicate the synergetic or additive effect of immunotherapy with [radiotherapy],” the authors noted. “The improved OS in patients who received [radiotherapy] plus immunotherapy may be associated with the abscopal effect of [radiotherapy].”

“For patients with significant extracranial disease, the addition of immunotherapy may improve survival by controlling extracranial disease,” the authors continued. “However, for those without or with minimal extracranial disease, the association of immunotherapy with survival will be mediated through the control of [brain metastases], which will be influenced by the drug permeability of [blood-brain barrier].”

Importantly though, this study lacked data regarding the cause of death, type of immunotherapy, information regarding chemotherapy regimens, ascertainment basis, and also included incomplete data. Additionally, the immunotherapy group represented only 5.7% of patients who received definitive surgery of the primary tumor site, indicating that it is a highly select group of patients with brain metastases and many individuals within this group may have been enrolled in clinical trials.

According to researchers, the collective study findings “warrant future clinical trials investigating the association of chemotherapy, [radiotherapy], and chemoradiation combined with immunotherapy with the survival of patients who receive definitive surgery of the primary tumor.”

Reference:

Amin S, Baine MJ, Meza JL, Lin C. Association of Immunotherapy With Survival Among Patients With Brain Metastases Whose CancerWas Managed With Definitive Surgery of the Primary Tumor. JAMA Network Open. doi: 10.1001/jamanetworkopen.2020.15444