Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
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DOI：
10.1056/nejmoa1910836
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发表时间：
2019-10-17
影响因子：
158.5
通讯作者：
Wolchok, J. D.
中科院分区：
文献类型：
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作者：
Larkin, J.;Chiarion-Sileni, V.;Wolchok, J. D.
在一项涉及晚期黑色素瘤患者的试验中，Nivolumab加ipilimumab或单独使用Nivolumab比单独使用ipilimumab导致更长的无进展生存期和总生存期。我们现在报告试验的5年结局。方法我们将既往未经治疗的晚期黑色素瘤患者随机分配接受以下方案之一：（剂量为1 mg/kg体重）加伊匹单抗（3 mg/kg），每3周给药一次，共给药4次，然后是纳武利尤单抗（nivolumab）（每2周3 mg/kg）; nivolumab（每2周每公斤3 mg）加伊匹单抗匹配的安慰剂;或伊匹单抗（每3周每公斤3 mg，共4剂）加nivolumab匹配的安慰剂。两个主要终点是nivolumab + ipilimumab组和nivolumab组与ipilimumab组相比的无进展生存期和总生存期。结果随访60个月以上，中位生存期大于60.0个月nivolumab + ipilimumab组的平均生存时间为36.9个月（中位数未达到），nivolumab组为36.9个月，ipilimumab组为19.9个月（纳武单抗加伊匹单抗与伊匹单抗的死亡风险比为0.52;纳武单抗与伊匹单抗的死亡风险比为0.63）。nivolumab + ipilimumab组的5年总生存率为52%，nivolumab组为44%，而ipilimumab组为26%。在nivolumab + ipilimumab或nivolumab单独治疗期间或之后，未观察到健康相关生活质量的持续恶化。未观察到新的晚期毒性作用。结论在晚期黑色素瘤患者中，接受nivolumab + ipilimumab或nivolumab单药治疗的患者5年持续长期总生存率高于接受ipilimumab单药治疗的患者，接受含nivolumab方案的患者生活质量无明显下降。
Background Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial. Methods We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group. Results At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 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, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted. Conclusions Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab.