Safe Integration of Encorafenib plus Binimetinib with Stereotactic Radiosurgery for Melanoma Brain Metastases: a Case Report.

Background: Melanoma brain metastases represents a significant clinical challenge, frequently associated with high morbidity and mortality. Recent advancements in neuroimaging, radiation therapy, and targeted systemic therapies, specifically BRAF and MEK inhibitors, have improved the management of this condition. Nevertheless, the optimal therapeutic approach for melanoma brain metastases remains a subject of ongoing debate, with no universally accepted treatment protocol. The combination of stereotactic radiosurgery with targeted therapy using encorafenib and binimetinib in patients harboring BRAF V600E mutation holds therapeutic promise but requires careful toxicity management to ensure both safety and efficacy.

Case Report: A 61-year-old male with metastatic BRAF V600E-mutated melanoma presented with a 20 mm brain metastasis in the right occipital lobe, manifesting as acute-onset diplopia. The patient was undergoing systemic therapy with encorafenib and binimetinib for metastatic lung involvement. Brain MRI revealed a metastatic lesion with surrounding edema. To minimize the risk of overlapping toxicities, a treatment strategy was devised, combining stereotactic radiosurgery with a temporary cessation of targeted therapy. Stereotactic radiosurgery was administered at a total dose of 27 Gy in three fractions, with enco-rafenib and binimetinib paused 24 hours prior to, and resumed 24 hours following, the radiosurgery. Following treatment, the patient's diplopia resolved completely, and a follow-up MRI two months later demonstrated near-total regression of the brain metastasis. At 30 months post-treatment, the patient remained free from recurrence and continued systemic therapy with excellent tolerance and no reported adverse effects.

Conclusions: This case demonstrates the efficacy and safety of combining stereotactic radiosurgery with encorafenib and binimetinib for managing melanoma brain metastases with BRAF V600E mutation. This approach provided effective disease control, as evidenced by symptom resolution, near-complete regression on MRI, and sustained remission at 30 months, with no adverse effects observed. Further studies are needed to establish standardized protocols for optimizing outcomes in this patient population.