Information on the role of radiotherapy in anti-PD-1 monoclonal antibody-treated melanoma patients is limited. We report on a prospective cohort of advanced melanoma patients treated simultaneously with radiotherapy and anti-PD-1 therapy between 01/01/15 and 30/06/16. Tumor evaluations (RECIST 1.1) were performed every 3 months on radiated and non-radiated lesions. Twenty-five advanced melanoma patients (64% AJCC stage IV M1c, 64% on second-line treatment or more, 60% with elevated LDH serum levels) were included. Radiotherapy was performed early (median: 24 days) after the first anti-PD-1 dose in 15 patients with rapidly progressing symptomatic lesion(s) or later (median: 5.4 months) in 10 patients with progressive disease (PD) despite PD-1 blockade. Radiotherapy was limited to one organ in 24 patients and consisted mainly of hypo-fractioned radiotherapy (median dose 26 Gy in 3–5 fractions, 17 patients) or brain radiosurgery (5 patients). Median follow-up after first anti-PD-1 dose was 16.9 m (range 2.7-27.4), with 44% of patients alive at last follow-up. For radiated lesions, rates of complete (CR), partial (PR) responses, stable disease (SD) or PD were 24%, 12%, 24%, and 32%, respectively. For non-radiated lesions, rates of CR, PR, SD, and PD were 20%, 19%, 12%, and 40%, respectively. Responses achieved after radiotherapy for radiated and non-radiated areas were correlated (Pearson correlation r: 0.89, P<0.0001) suggesting an abscopal effect. Five patients with CR remained disease-free after discontinuation of anti-PD-1 for a median of 9.5 months. No unusual adverse event was recorded. Hypo-fractionated radiotherapy may enhance efficacy of anti-PD1 therapy in difficult-to-treat patients. Controlled studies are needed.

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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.

9537 Background: Radiotherapy (Rx) and anti-PD-1 mAb are potentially synergistic. No study has tested this combination only in pts who failed on anti-PD-1 mAb, which allows to assess the abscopal effect. We evaluated this combination in a cohort of advanced melanoma pts after failure of anti-PD-1 monotherapy. Methods: Analysis of a prospective database in a referral center searching for advanced melanoma pts with confirmed (2 CT-scans) progressive (PD) or stable (SD) disease on anti-PD-1 monotherapy, who later received concurrent Rx without modification of anti-PD-1 mAb regimen. Radiologists performed independent tumor evaluations (RECIST 1.1) every 3 m, both on radiated and non-radiated lesions, with abscopal effect defined as a partial (PR) or complete (CR) response outside radiated fields. Results: 26 pts (21 achieving PD, 5 SD, 10 pt ≥3 involved organs), mean age 70 Y, were included. Anti-PD-1 mAb was first line in 50% of pts. Rx, consisting of hypofractionnated Rx (3-5 sessions, 26 Gy), standard palliative Rx, or gamma-knife in respectively 23, 2, and 1 pts, was begun on a single site in 73% of pts or on 2 sites after a median of 5 m after beginning anti-PD-1 mAb. Median follow-up after onset of anti-PD-1 mAb was 17 (7-35) m, with 65% of pts alive at last follow-up. Best response was 7 CR (27%, including CR in 4 pts with prior PD) 1 PR, 3 SD (12%), 15 PD (58%). Abscopal effect was seen in 10 pts (38%). No correlation between the occurrence of CR and BRAF/NRAS mutation status, number of metastatic sites, presence or absence of brain metastases, and LDH level was seen. Anti-PD-1 mAb could be discontinued in 6 pts with CR, without relapse to date. No unusual adverse event was recorded. Conclusions: In pts who have previously failed on anti-PD-1 mAb, obtaining with concurrent Rx and without modifying anti-PD-1 mAb, CR or PR in 30% of pts, median OS not achieved, and abscopal effect in > 1/3 of pts is probably not due only to late efficacy of anti-PD-1 mAb but suggests a synergy with RT. Release after radiation of tumor neoantigens may stimulate immune response. Hypo-fractionated radiotherapy may enhance anti-PD1 monotherapy efficacy in melanoma pts who failed on anti-PD-1 mAb. Controlled studies are needed.

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