PD-1抗体联合CTLA-4抗体,缔造抗癌新纪录
  • 945例初治晚期黑色素瘤患者1:1:1随机,纳武单抗与伊匹单抗联合,或单药,根据PD-L1表达、BRAF突变和晚期状态进行分层;
  • 至少随访36个月,联合组中位OS未达到,纳武单抗组为37.6个月,伊匹单抗组为19.9个月,联合组对伊匹的死亡风险HR0.55,纳武对伊匹的HR0.65,3年总体生存率分别为58%、52%和34%;
  • 3或4度治疗相关性不良事件发生率分别为59%、21%和28%;
  • 与伊匹单抗单药相比,联合治疗或纳武单抗单药治疗晚期黑色素瘤,OS明显改善。
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Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

纳武单抗联合伊匹单抗治疗晚期黑色素瘤患者的总体生存期

10.1056/NEJMoa1709684

2017-09-11, Article

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Background: Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial.
Methods: We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. The two primary end points were progressionfree survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group.
Results: At a minimum follow-up of 36 months, the median overall survival had not been reached in the nivolumab-plus-ipilimumab group and was 37.6 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001]; hazard ratio for death with nivolumab vs. ipilimumab, 0.65 [P<0.001]). The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group. The safety profile was unchanged from the initial report. Treatment-related adverse events of grade 3 or 4 occurred in 59% of the patients in the nivolumab-plus-ipilimumab group, in 21% of those in the nivolumab group, and in 28% of those in the ipilimumab group.
Conclusions: Among patients with advanced melanoma, significantly longer overall survival occurred with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.)

First Authors:
JD Wolchok

Correspondence Authors:
JD Wolchok

All Authors:
Jedd D Wolchok,Vanna Chiarion-Sileni,Rene Gonzalez,Piotr Rutkowski,Jean-Jacques Grob,C Lance Cowey,Christopher D Lao,John Wagstaff,Dirk Schadendorf,Pier F Ferrucci,Michael Smylie,Reinhard Dummer,Andrew Hill,David Hogg,John Haanen,Matteo S Carlino,Oliver Bechter,Michele Maio,Ivan Marquez-Rodas,Massimo Guidoboni,Grant McArthur,Celeste Lebbé,Paolo A Ascierto,Georgina V Long,Jonathan Cebon,Jeffrey Sosman,Michael A Postow,Margaret K Callahan,Dana Walker,Linda Rollin,Rafia Bhore,F Stephen Hodi,James Larkin

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