FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma
FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma
复制标题
DOI：
10.1158/1078-0432.ccr-16-0714
复制
发表时间：
2017-07-15
影响因子：
11.5
通讯作者：
Pazdur, Richard
中科院分区：
文献类型：
--
作者：
Beaver, Julia A.;Theoret, Marc R.;Pazdur, Richard
2015年11月23日，FDA批准纳武单抗（OPDIVO;百时美施贵宝）作为一线治疗BRAF（V600）野生型、不可切除或转移性黑色素瘤患者的单药。在美国以外进行的一项国际、双盲、随机（1：1）试验将418名患者分配为每2周静脉注射nivolumab 3 mg/kg（n = 210）或每3周静脉注射达卡巴嗪1，000 mg/m2（n = 208）。允许符合方案规定标准的疾病进展患者（与每个试验组的25%相似）以设盲方式继续接受分配的治疗，直至记录到进一步的疾病进展。与达卡巴嗪组相比，纳武利尤单抗组的总生存期在统计学上显著改善[风险比（HR），0.42; 95%置信区间（CI），0.30-0.60; P < 0.0001]。nivolumab组的无进展生存期也有统计学显著改善（HR，0.43; 95%CI，0.34-0.56; P < 0.0001）。纳武利尤单抗最常见的不良反应（>= 20%）是疲劳、腹泻、便秘、恶心、肌肉骨骼疼痛、皮疹和瘙痒。与达卡巴嗪相比，纳武利尤单抗表现出有利的获益-风险特征，支持定期批准;然而，目前尚不清楚疾病进展后的治疗是否有助于纳武利尤单抗的总体临床获益。(C)2017年AACR。
On November 23, 2015, the FDA approved nivolumab (OPDIVO; Bristol-Myers Squibb) as a single agent for the first-line treatment of patients with BRAF(V600) wild-type, unresectable or metastatic melanoma. An international, double-blind, randomized (1: 1) trial conducted outside of the United States allocated 418 patients to receive nivolumab 3 mg/kg intravenously every 2 weeks (n = 210) or dacarbazine 1,000 mg/m(2) intravenously every 3 weeks (n = 208). Patients with disease progression who met protocol-specified criteria (similar to 25% of each trial arm) were permitted to continue with the assigned treatment in a blinded fashion until further disease progression is documented. Overall survival was statistically significantly improved in the nivolumab arm compared with the dacarbazine arm [hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.30-0.60; P < 0.0001]. Progression-free survival was also statistically significantly improved in the nivolumab arm (HR, 0.43; 95% CI, 0.34-0.56; P < 0.0001). The most common adverse reactions (>= 20%) of nivolumab were fatigue, diarrhea, constipation, nausea, musculoskeletal pain, rash, and pruritus. Nivolumab demonstrated a favorable benefit-risk profile compared with dacarbazine, supporting regular approval; however, it remains unclear whether treatment beyond disease progression contributes to the overall clinical benefit of nivolumab. (C) 2017 AACR.