First-line stereotactic radiosurgery combined with systemic targeted and immune checkpoint inhibitor therapy in melanoma patients with newly diagnosed brain metastases.

Abstract

e13577 Background: Of solid tumors, melanoma has the highest propensity for central nervous system spread with historic median survivals of 5-8 months following brain metastasis diagnosis. We evaluated the impact of systemic BRAF targeted and immune checkpoint inhibitor (ICI) therapies on survival outcomes in patients receiving stereotactic radiosurgery (SRS) for melanoma brain metastases (MBM) and assessed patient treatment burden associated with prolonged survival. Methods: We retrospectively reviewed the demographics, disease characteristics, therapeutic regimens, overall survival, and first-year cumulative incidence of comorbid disease for patients with de novo MBM treated between 2013 and 2017 at a major melanoma referral center. Results: Among 123 newly diagnosed MBM patients:65% were male, 24%were 50 years old or less, 50% were BRAF mutated, 63% had multiple intracranial lesions at diagnosis . Locally, 73% received SRS as first-line treatment.Systemically, 73% received ICI, 46% received BRAF targeted therapy, and 12% received neither. With median follow up of 11 months (mo), totalcohort median OS was 13.2 mo, 20.5 mo for BRAF mutated patients, 10.8 mo for BRAF wild-type patients. Median OS for first-line SRS was 31.0 mo (47% 3-year OS) when combined with both ICI and BRAF targeted therapy, 17.5 mo (31% 3-year OS) when combined with ICI monotherapy, and 6.1 mo (22% 3-yr OS) with neither systemic therapy. SRS and BRAF targeted therapy were associated with improved OS. BRAF status, ICI therapy, intratumoral hemorrhage were not significant prognosticators for OS.At one-year follow-up, comorbid conditions with the greatest cumulative incidence were fatigue, nausea, intracranial hemorrhage, deep vein thrombosis, major depressive disorder, and pneumonia. Patients averaged one inpatient visit every 4.5 mo (1 week average length of stay), and 2 advanced imaging studies (MR/CT/PET-CT) per month following MBM diagnosis. Conclusions: In one of the largest reported MBM series, survival has improved markedly for patients receiving first-line brain radiosurgery combined with BRAF targeted therapies and immunotherapies. Simultaneously, longer life expectancy comes with increasing incidences of comorbid conditions reflecting an evolving complexity of and need for coordination of care for patients with MBM.