Safety and results of anti-PD1 combined with radiosurgery for the treatment of melanoma brain metastases.

Abstract

9552 Background: Anti-PD1 are now pivotal in the treatment of metastatic melanoma (MM). Some concerns have emerged regarding the risk/benefit ratio of their combination with stereotactic radiosurgery. Methods: Retrospective assessment of the interaction between Gamma-Knife radiosurgery (GKRS) and anti-PD1 in terms of toxicity and OS in mm patients (pts) with BM. Patients were included if they were under anti-PD1 (PRE) at time of GKRS, or if they had started anti-PD1 concomitantly with GKRS (CO), or had received anti-PD1 within 3 months after GKRS (POST). Results: Among 47 pts who received GKRS and anti-PD1 during their disease course, 35 fulfilled PRE or CO or POST criteria (anti PD1 1st line therapy in 10 pts and 2d or more in 25 pts). One pt died before radiological evaluation. GKRS targeted a single BM in 10 pts and multiple BMs in 24 (max 19 BMs). Out of the 128 BMs treated, 6 cases of increase of preexisting edema (4.7%) and 8 hemorrhages (6.25%) occurred in 12 pts, but only 5 events (5%) were regarded as Adverse Radiation effects (ARE), being symptomatic in 3 pts (8% of pts). One BM had to be resected because of the occurrence of a symptomatic hemorrhage with hemiparesis 9 month after treatment. Median follow- up from GKRS was 13.7 mths. Median overall survival (OS) from GKRS and 1st BM were 14.8 and 26.5 mths respectively, with 6 and 12 mths 0S rates from GKRS of 65.7% and 57%, respectively. Local failure was observed in 5 pt. Median time to new BM was 12.6 mths. There was no significant difference in outcomes in pts, depending on PRE, CO and POST conditions. Conclusions: In this series, the largest to date of pts with BMs treated by GKRS and anti-PD1,ARE were within the expected range and survival rates appear promising. Given the natural propensity of MM-BMs for bleeding and edema our data do not support an increased risk with the combination of GKRS and anti-PD1. Regarding the timing between anti-PD1 administration and GKRS our data do not support a higher efficacy or higher toxicity among the 3 following potential mechanisms: immuno- sensitization to radiation (PRE), immuno-radio direct synergy (CO) or radiosensitization to immunotherapy (POST).