Therapies that target elements of the immune system or certain pathways active in cancer cells, in combination with radiation therapy, may work better than chemotherapy for patients with melanoma brain metastases, according to a research report from the Lee Moffitt Cancer Center and Research Institute.
The study “Clinical Outcomes Of Melanoma Brain Metastases Treated With Stereotactic Radiosurgery And Anti-PD-1 Therapy, Anti-CTLA-4 Therapy, BRAF/MEK Inhibitors, BRAF Inhibitor, Or Conventional Chemotherapy,” was published Annals of Oncology.
Current treatment options for melanoma brain metastases include surgery, whole brain radiation, and focused radiation (stereotactic radiation) therapies. The treatments can be combined with conventional chemotherapy, but the latter has failed to provide positive outcomes to patients with the disease.
Previous research suggested that therapies specifically targeting components of the immune system may be beneficial to patients with melanoma brain metastases. For example, the anti-PD-1 immunotherapy agent Opdivo (nivolumab), has been shown effective and safe in patients in combination with stereotactic radiation therapy.
Karen Ahmed and colleagues from the Moffitt Cancer Center aimed further to see if combining radiation therapy with treatments directed against the immune system or active pathways in cancer cells would improve patient outcome, compared to conventional chemotherapy plus radiotherapy.
The researchers found that targeted treatments were better able to control tumor growth outside the irradiated field in the brain than standard chemotherapy. Patients who were treated with radiation therapy after anti–PD-1 therapy or BRAF/MEK inhibitors had the best tumor control out of all treatment groups.
Therapies that target PD-1 or CTLA-4 are meant to enhance the immune system’s ability to recognize and target tumor cells, whereas BRAF and MEF inhibitors directly target pathways that are usually mutated and highly activated in melanoma cells.
Results indicated that patients treated with one of these targeted therapies had better outcomes than those who received conventional chemotherapy. In particular, those who received radiation therapy after BRAF/MEK inhibitors or anti-PD-1 therapy had the best tumor control of all.
The patients also had the highest improved survival of all groups, with one-year overall survival rates of 65% for the BRAF/MEK inhibitors group, 48% for the anti-PD-1 therapy, and 10% for the conventional chemotherapy group.
“These results reveal that in patients with melanoma brain metastases, anti-PD-1 therapy and BRAF/MEK inhibitors alongside stereotactic radiosurgery offer optimal control of disease spread in the brain,” said Ahmed in a news release. “Although future randomized studies will be necessary to confirm the benefit of adding anti-PD-1 agents and BRAF/MEK inhibitors to stereotactic radiation to improve the outcomes of patients with melanoma brain metastases, these results are encouraging.”