Clinical Outcomes of Melanoma Brain Metastases Treated with Stereotactic Radiosurgery and Anti-PD-1 Therapy, Anti-CTLA-4 Therapy, BRAF/MEK Inhibitors, BRAF Inhibitor, or Conventional Chemotherapy
Menée sur 96 patients atteints d'un mélanome avec métastases cérébrales traitées entre 2007 et 2015, cette étude évalue l'efficacité, du point de vue du contrôle des métastases cérébrales, de la survie sans progression systémique et de la survie globale, d'une radiochirurgie stéréotaxique en combinaison avec un agent anti-PD-1 ou anti-CTLA-4, un inhibiteur de BRAF/MEK ou de BRAF, ou une chimiothérapie standard
Background : The effect of immunologic and targeted agents on intracranial response rates in patients with melanoma brain metastases (MBMs) is not yet clearly understood. This report analyzes outcomes of intact MBMs treated with single session SRS and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAFi, or conventional chemotherapy. Patients and Methods : Patients were included if MBMs were treated with single session SRS within 3 months of receiving systemic therapy. The primary endpoint of this study was distant MBM control. Secondary endpoints were local MBM control defined as a >20% volume increase on follow up MRI, systemic progression free survival (sPFS), overall survival (OS) from both SRS and cranial metastases diagnosis, and neurotoxicity. Images were reviewed alongside two neuro-radiologists at our institution. Results : Ninety-six patients were treated to 314 MBM over 119 SRS treatment sessions between 01/2007 and 08/2015. No significant differences were noted in age (p=0.27), gender (p=0.85), treated gross tumor volume (GTV) (p =0.26), or the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) (p =0.51) between the treatment cohorts. Twelve month KM distant MBM control rates were 38%, 21%, 20%, 8%, and 5% (p =0.008) for SRS with anti-PD-1 therapies, anti-CTLA-4 therapy, BRAF/MEKi, BRAFi, and conventional chemotherapy, respectively. No significant differences were noted in the Kaplan-Meier (KM) local MBM control rates amongst treatment groups, (p =0.25). Treatment with anti-PD-1 therapy, anti-CTLA-4 therapy, or BRAF/MEKi significantly improved OS on both univariate and multivariate analyses when compared to conventional chemotherapy. Conclusions : In our institutional analysis of patients treated with SRS and various systemic immunologic and targeted melanoma agents, significant differences in distant MBM control and OS are noted. Prospective evaluation of the potential synergistic effect between these agents and SRS is warranted.