Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.
Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.
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DOI：
10.1056/nejmoa1709684
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发表时间：
2017-10-05
期刊：
影响因子：
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通讯作者：
Larkin J
中科院分区：
文献类型：
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作者：
Wolchok JD;Chiarion-Sileni V;Gonzalez R;Rutkowski P;Grob JJ;Cowey CL;Lao CD;Wagstaff J;Schadendorf D;Ferrucci PF;Smylie M;Dummer R;Hill A;Hogg D;Haanen J;Carlino MS;Bechter O;Maio M;Marquez-Rodas I;Guidoboni M;McArthur G;Lebbé C;Ascierto PA;Long GV;Cebon J;Sosman J;Postow MA;Callahan MK;Walker D;Rollin L;Bhore R;Hodi FS;Larkin J
在一项涉及晚期黑色素瘤患者的3期试验中，纳武利尤单抗联合伊匹木单抗相较于单独使用伊匹木单抗，无进展生存期更长，客观缓解率更高。我们在此报告该试验的3年总生存期结果。
我们按照1:1:1的比例将先前未经治疗的晚期黑色素瘤患者随机分组，分别接受以下治疗：纳武利尤单抗（剂量为每千克体重1毫克）联合伊匹木单抗（剂量为每千克体重3毫克），每3周给药一次，共4次，之后纳武利尤单抗以每千克体重3毫克的剂量每2周给药一次；纳武利尤单抗以每千克体重3毫克的剂量每2周给药一次加安慰剂；伊匹木单抗以每千克体重3毫克的剂量每3周给药一次，共4次加安慰剂，直至疾病进展、出现不可接受的毒性作用或患者撤回同意。随机分组根据程序性死亡配体1（PD - L1）状态、BRAF突变状态和转移阶段进行分层。两个主要终点是纳武利尤单抗联合伊匹木单抗组以及纳武利尤单抗组相较于伊匹木单抗组的无进展生存期和总生存期。
在至少36个月的随访中，纳武利尤单抗联合伊匹木单抗组的中位总生存期尚未达到，纳武利尤单抗组为37.6个月，而伊匹木单抗组为19.9个月（纳武利尤单抗联合伊匹木单抗相较于伊匹木单抗的死亡风险比为0.55[P<0.001]；纳武利尤单抗相较于伊匹木单抗的死亡风险比为0.65[P<0.001]）。3年总生存率在纳武利尤单抗联合伊匹木单抗组为58%，在纳武利尤单抗组为52%，而在伊匹木单抗组为34%。安全性特征与初次报告相比无变化。3级或4级治疗相关不良事件在纳武利尤单抗联合伊匹木单抗组的患者中发生率为59%，在纳武利尤单抗组为21%，在伊匹木单抗组为28%。
在晚期黑色素瘤患者中，纳武利尤单抗联合伊匹木单抗或纳武利尤单抗单药治疗的总生存期明显长于单独使用伊匹木单抗。（由百时美施贵宝等资助；CheckMate 067，ClinicalTrials.gov编号NCT01844505）
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. 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 progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group. 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. 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.)