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

IF 7.6 1区 医学 Q1 ONCOLOGY European Journal of Cancer Pub Date : 2025-01-22 DOI:10.1016/j.ejca.2025.115256
Jérôme Doyen , Anne Dompmartin , Coralie Cruzel , Dinu Stefan , Jean-Philippe Arnault , Alexandre Coutte , Alexandra Picard-Gauci , Sandrine Mansard , Baptiste Gleyzolle , Eric Fontas , Elodie Long-Mira , Xavier Mirabel , Laurent Mortier , Henri Montaudié
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Abstract

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.
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来源期刊
European Journal of Cancer
European Journal of Cancer 医学-肿瘤学
CiteScore
11.50
自引率
4.80%
发文量
953
审稿时长
23 days
期刊介绍: The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.
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