Nivolumab and hypofractionated radiotherapy in patients with advanced melanoma: a phase 2 trial
Mené sur 64 patients atteints d'un mélanome de stade avancé (durée médiane de suivi : 23,5 mois ; âge médian : 68 ans ; 67 % d'hommes), cet essai multicentrique de phase II évalue l'efficacité, du point de vue de la survie globale à 1 an, d'un traitement combinant radiothérapie hypofractionnée et nivolumab
Background: 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. Methods: 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). Results: 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). Conclusions: 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.