Intracranial Treatment in Melanoma Patients with Brain Metastasis Is Associated with Improved Survival in the Era of Immunotherapy and Anti-BRAF Therapy

SIMPLE SUMMARY: Melanoma is one of the top three causes of brain metastases, which is still a poor prognostic factor of overall survival. Novel systemic therapies have changed the prognosis of patients and the place of local intracranial treatment, surgery and/or radiotherapy in this era remains unclear. We evaluated the incidence of brain metastasis in melanoma patients in a large retrospective French cohort who received immunotherapy and/or targeted therapy for and identified prognostic factors. Local intracranial treatment is statistically significantly associated with improved overall survival through comparable groups in terms of age, number of BM, BRAF status and systemic treatment. The question of administering local treatment, even for more than one metastasis, such as stereotactic radiotherapy, should be addressed at the diagnosis of brain metastasis while introducing systemic treatment such as immunotherapy. Three prospective trials evaluating additional SRT in combination to ipilimumab and nivolumab association are ongoing. ABSTRACT: Metastatic melanoma patients are at high risk of brain metastases (BM). Although intracranial control is a prognostic factor for survival, impact of local (intracranial) treatment (LT), surgery and/or radiotherapy (stereotactic or whole brain) in the era of novel therapies remains unknown. We evaluated BM incidence in melanoma patients receiving immune checkpoint inhibitors (ICI) or anti-BRAF therapy and identified prognostic factors for overall survival (OS). Clinical data and treatment patterns were retrospectively collected from all patients treated for newly diagnosed locally advanced or metastatic melanoma between May 2014 and December 2017 with available BRAF mutation status and receiving systemic therapy. Prognostic factors for OS were analyzed with univariable and multivariable survival analyses. BMs occurred in 106 of 250 eligible patients (42.4%), 64 of whom received LT. Median OS in patients with BM was 7.8 months (95% CI [5.4–10.4]). In multivariable analyses, LT was significantly correlated with improved OS (HR 0.21, p < 0.01). Median OS was 17.3 months (95% CI [8.3–22.3]) versus 3.6 months (95% CI [1.4–4.8]) in patients with or without LT. LT correlates with improved OS in melanoma patients with BM in the era of ICI and anti-BRAF therapy. The use of LT should be addressed at diagnosis of BM while introducing systemic treatment.