Efficacy of late concurrent hypofractionated radiotherapy in advanced melanoma patients failing anti-PD-1 monotherapy

Advanced melanoma patients who failed anti-PD-1 therapy have limited options. We analyzed a cohort of 133 advanced melanoma patients receiving anti-PD-1 monotherapy in a referral center between April 2015 and December 2017, and included the 26 patients with confirmed progressive (PD) or stable disease who received additional radiotherapy with an unmodified anti-PD-1 mAb regimen. Tumor evaluations were done on radiated and nonradiated (RECIST 1.1) lesions, with abscopal effect defined as a partial (PR) or complete response (CR) outside radiated fields. Primary endpoint was the CR + PR rate in radiated + nonradiated lesions. Secondary endpoints were progression-free survival (PFS), melanoma-specific survival (MSS) and safety. First late radiotherapy, consisting of hypofractionated radiotherapy (3-5 sessions, 20-26 Gy), standard palliative radiotherapy or brain radiosurgery was begun after a median of 6.3 months of anti-PD-1 in 23, 2 and 1 patient(s), respectively. Best response was 8 (31%) CR, 2 (8%) profound PR allowing surgical resection of remaining metastases and 16 (62%) PD. Abscopal effect was seen in 35% of patients. Median PFS and MSS since anti-PD-1 initiation was 15.2 [95% CI: 8.0 not achieved (na)] and 35.3 [95% CI: 18.5 na] months, respectively. PFS curves seemed to achieve a plateau. We discontinued anti-PD-1 therapy in 9/10 of patients with no residual evaluable disease and observed one relapse after a median of 10 months off anti-PD1-therapy. No unusual adverse event was recorded. Limitations of the study include its retrospective nature and limited size. Hypofractionated radiotherapy may enhance anti-PD1 monotherapy efficacy in patients who previously failed anti-PD-1 therapy. Controlled studies are needed.