The Next Frontier: Radiotherapy Plus Immunotherapy for Melanoma Brain Metastases

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The combination of radiotherapy and immunotherapy for brain metastases is promising, though toxicity and timing are poorly-understood factors.
The combination of radiotherapy and immunotherapy for brain metastases is promising, though toxicity and timing are poorly-understood factors.

The prognosis of patients with melanoma brain metastases is poor, though early clinical studies suggest that the combination of radiotherapy and immunotherapy may be an effective new approach for this population.

“The combination of immunotherapy and radiotherapy can open new frontiers for patients with cancer, but there is still a lot to do. It is necessary to make all possible efforts to include patients in prospective trials, which will ensure strong and reliable data,” Marta Scorsetti, MD, associate professor of diagnostic imaging and radiotherapy in the department of biomedical sciences at Humanitas University, and the director of radiotherapy and radiosurgery at Humanitas Research Hospital in Milan, Italy, told Cancer Therapy Advisor.

The treatments of melanoma brain metastases historically included surgery or radiotherapy, both as whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS), though neither have long-term success. Surgical removal of brain metastases can benefit patients who have neurologic symptoms and who have limited sites of disease. Although WBRT can improve intracranial disease, it is associated with cognitive decline. In contrast, SRS provides high-dose to precise areas in the brain with a low incidence of neurologic toxicity.1

The options for systemic therapy of melanoma recently expanded with the addition of targeted and immunotherapies. A major problem in the setting of brain metastasis, however, is the blood-brain barrier, which prevents many of these agents, as well as chemotherapy, from reaching the brain.

Research demonstrates that activated T-cells are able to cross the blood-brain barrier, raising the possibility that checkpoint inhibitors will be effective against melanoma brain metastasis.2,3 Several small studies found promising results with ipilimumab, an anti-CTLA-4 antibody, including 2 phase 2 trials that demonstrated a complete response rate of approximately 25%.4,5,6,7 Phase 2 trials with other checkpoint inhibitors are ongoing.

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