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.