• 906例15岁以上手术完全切除的IIIB、IIIC或IV期黑色素瘤患者,1:1随机分组,接受纳武单抗或伊匹单抗,持续治疗1年、疾病复发、不可耐受毒性或撤回知情同意;
  • 至少随访18个月,两组12个月的无复发生存率(RFS)分别为70.5%和60.8%,HR 0.65;
  • 治疗相关的3或4度分别为14.AE4%和45.9%,AE导致的治疗终止分别为9.7%和42.6%;
  • 与伊匹单抗相比,纳武单抗辅助治疗明显改善完全切除的IIIB、IIIC或IV期黑色素瘤患者的RFS,且3或4度AE发生率低。

Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma



2017-09-10, Article

Abstract & Authors:展开

Background: Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma.
Methods: In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-to-treat population.
Results: At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% (95% confidence interval [CI], 66.1 to 74.5) in the nivolumab group and 60.8% (95% CI, 56.0 to 65.2) in the ipilimumab group (hazard ratio for disease recurrence or death, 0.65; 97.56% CI, 0.51 to 0.83; P<0.001). Treatment-related grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment.
Conclusions: Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 238 ClinicalTrials.gov number, NCT02388906; Eudra-CT number, 2014-002351-26.)

First Authors:
J Weber

Correspondence Authors:
J Weber

All Authors:
Jeffrey Weber,Mario Mandala,Michele Del Vecchio,Helen J Gogas,Ana M Arance,C Lance Cowey,Stéphane Dalle,Michael Schenker,Vanna Chiarion-Sileni,Ivan Marquez-Rodas,Jean-Jacques Grob,Marcus O Butler,Mark R Middleton,Michele Maio,Victoria Atkinson,Paola Queirolo,Rene Gonzalez,Ragini R Kudchadkar,Michael Smylie,Nicolas Meyer,Laurent Mortier,Michael B Atkins,Georgina V Long,Shailender Bhatia,Celeste Lebbé,Piotr Rutkowski,Kenji Yokota,Naoya Yamazaki,Tae M Kim,Veerle de Pril,Javier Sabater,Anila Qureshi,James Larkin,Paolo A Ascierto,