Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, U.S.A.
Br J Dermatol. 2018 Aug;179(2):296-300. doi: 10.1111/bjd.16785. Epub 2018 Jun 5.
To show whether either nivolumab in combination with ipilimumab or nivolumab monotherapy vs. ipilimumab monotherapy extends overall survival (OS) or progression-free survival (PFS) in adults with previously untreated, advanced melanoma.
The trial was conducted at 137 sites in 21 countries. Randomization (n = 945; 1 : 1 : 1 ratio) was stratified according to metastasis stage, BRAF mutation status and programmed death ligand 1 status.
Adults were randomized to one of the following: nivolumab plus ipilimumab every 3 weeks for four doses, followed by nivolumab every 2 weeks; nivolumab every 2 weeks plus placebo; or ipilimumab every 3 weeks for four doses plus placebo. Treatment was continued until progression, unacceptable toxicity or withdrawal.
OS, PFS and objective response rate were determined. Patients were also assessed for adverse events. The primary end points of interest were OS and PFS, comparing either the nivolumab plus ipilimumab group or the nivolumab-only group with the patients treated with ipilimumab only.
At 3 years, the OS rates were 58%, 52% and 34% for the nivolumab plus ipilimumab, the nivolumab monotherapy and the ipilimumab monotherapy groups, respectively. For the nivolumab plus ipilimumab group, the median OS was not reached at the time of analysis. For the nivolumab-only group, the median OS was 37·6 months, and the ipilimumab-only group had a median OS of 19·9 months. The hazard ratio for death was 0·55 [95% confidence interval (CI) 0·45-0·69; P < 0·001] comparing nivolumab plus ipilimumab with ipilimumab, and 0·65 (95% CI 0·53-0·80; P < 0·001) comparing nivolumab with ipilimumab. The PFS rates at 3 years were 39% for the nivolumab plus ipilimumab group, 32% for the nivolumab monotherapy group and 10% for the ipilimumab monotherapy group, with 95% CIs for the two nivolumab groups that did not overlap with that for ipilimumab alone.
Among patients with advanced melanoma, significantly longer OS and PFS occurred with the combination of nivolumab plus ipilimumab or with nivolumab alone compared with ipilimumab alone. Furthermore, survival outcomes favoured the nivolumab-containing groups over the ipilimumab group in subgroup analyses.
展示纳武利尤单抗联合伊匹单抗或纳武利尤单抗单药治疗与伊匹单抗单药治疗相比，是否能延长未经治疗的晚期黑色素瘤成人患者的总生存期（OS）或无进展生存期（PFS）。
该试验在 21 个国家的 137 个地点进行。根据转移阶段、BRAF 突变状态和程序性死亡配体 1 状态，将随机分组（n=945；1:1:1 比例）进行分层。
成人被随机分配到以下治疗组之一：纳武利尤单抗联合伊匹单抗每 3 周给药 4 次，随后每 2 周给药 1 次；纳武利尤单抗每 2 周给药 1 次，同时给予安慰剂；或伊匹单抗每 3 周给药 4 次，同时给予安慰剂。治疗持续到疾病进展、不可接受的毒性或停药。
评估 OS、PFS 和客观缓解率。还评估了患者的不良事件。主要关注的终点是 OS 和 PFS，比较纳武利尤单抗联合伊匹单抗组或纳武利尤单抗单药组与单独使用伊匹单抗组的疗效。
在 3 年时，纳武利尤单抗联合伊匹单抗组、纳武利尤单抗单药组和伊匹单抗单药组的 OS 率分别为 58%、52%和 34%。对于纳武利尤单抗联合伊匹单抗组，分析时未达到中位 OS。纳武利尤单抗单药组的中位 OS 为 37.6 个月，伊匹单抗单药组的中位 OS 为 19.9 个月。与伊匹单抗相比，纳武利尤单抗联合伊匹单抗组死亡风险比为 0.55（95%置信区间 0.45-0.69；P<0.001），纳武利尤单抗与伊匹单抗相比为 0.65（95%置信区间 0.53-0.80；P<0.001）。在 3 年时，纳武利尤单抗联合伊匹单抗组的 PFS 率为 39%，纳武利尤单抗单药组为 32%，伊匹单抗单药组为 10%，纳武利尤单抗单药组的两个 PFS 率与伊匹单抗单药组没有重叠。
在晚期黑色素瘤患者中，与单独使用伊匹单抗相比，纳武利尤单抗联合伊匹单抗或纳武利尤单抗单药治疗可显著延长 OS 和 PFS。此外，在亚组分析中，与伊匹单抗组相比，纳武利尤单抗组的生存结果更为有利。
