Advances in the systemic treatment of brain metastases in malignant melanoma

Abstract

Brain metastases are a significant negative prognostic factor, not only in malignant melanoma. With the development and availability of imaging methods, with progress in the field of neurosurgery, radiotherapy and especially with the advent of modern systemic treatment, the survival of these patients is significantly improving. The treatment of brain metastases requires a multidisciplinary approach. In a limited number of metastases, the treatment is based on neurosurgery and/or radiosurgery. We often combine the local method with modern systemic treatment based on immunotherapy with checkpoint inhibitors or targeted therapy with BRAF and MEK inhibitors. The best results have been achieved with the combination of immunotherapy (nivolumab and ipilimumab) in patients with asymptomatic brain metastases, although with significant immunerelated toxicity. Patients with symptomatic brain metastases are still problematic to treat effectively. A combination of targeted therapy and immunotherapy could improve their outcomes. However, knowledge from research into the tumor microenvironment in the brain will be crucial to help us overcome primary and secondary drug resistance.