Nivolumab and hypofractionated radiotherapy in patients with advanced melanoma: A phase 2 trial

Radiotherapy is thought to enhance anti-tumor immunity, particularly when delivered in a hypofractionated and multisite manner. Therefore, we investigated the effects of combining radiotherapy with nivolumab in patients with advanced melanoma. This was a multicenter, non-randomized, phase 2 trial that enrolled patients with treatment-naïve metastatic melanoma. They received nivolumab (240 mg / 2 weeks) plus radiotherapy (day 15, 6 Gy × 3). When feasible, one target from each organ was irradiated (no irradiation of all targets). The primary endpoint was 1-year overall survival (OS). This trial included 64 patients between March 2017 and July 2019. The median follow-up was 23.5 (2.3–43.8) months. The median age was 68 (35–95) years, patients were mostly male (67 %) with an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0 (72 %), stage IV-M1c disease (47 %), and were BRAF-wild-type (67 %). The 2-year OS and 1-year PFS rates were 65.2 % and 56 %, respectively (P = 0.22 and P = 0.03, vs. 58 % and 43 %, respectively, in the Checkmate 066 study). Thirty-seven (58 %) and twenty-seven (42 %) patients were irradiated at one and multiple targets, respectively. The ECOG-PS (1 vs. 0; HR = 3.5; P = 0.005) was an independent prognostic factor for OS. Irradiating more than one site and irradiating a smaller cumulative tumor volume tended to correlate with better outcome. Grade 3–4 treatment-related adverse events occurred in 21.9 % of the patients (no grade 5). Combined immunotherapy and hypofractionated radiotherapy did not improve survival compared to historical cohorts. The radiotherapy schedule needs to be optimized in order to improve these results. •Prospective data are missing about the impact of RT + IO in advanced melanoma.•64 patients were included in this phase II trial and received nivolumab with RTH.•Nivolumab + RTH did not improve survival compared to historical cohort.•Multisite irradiation tended to correlate with better outcome.•The radiotherapy schedule needs to be optimized in order to improve this strategy.