Pooled Analysis Safety Profile of Nivolumab and Ipilimumab Combination Therapy in Patients With Advanced Melanoma
Pooled Analysis Safety Profile of Nivolumab and Ipilimumab Combination Therapy in Patients With Advanced Melanoma
复制标题
DOI：
10.1200/jco.2016.72.1167
复制
发表时间：
2017-12-01
影响因子：
45.3
通讯作者：
Wolchok, Jedd D.
中科院分区：
文献类型：
--
作者：
Sznol, Mario;Ferrucci, Pier Francesco;Wolchok, Jedd D.
目的在晚期黑色素瘤患者中，将nivolumab（抗程序性死亡-1抗体）添加到ipilimumab（抗细胞毒性T细胞淋巴细胞相关4抗体）中可改善抗肿瘤反应和无进展生存期，但不良事件（AE）发生率较高。这项交叉黑色素瘤研究描述了批准的nivolumab加ipilimumab方案的安全性。（第一、二、三阶段）和III）包括患有晚期黑素瘤的患者，这些患者每3周接受至少一个剂量的纳武单抗1 mg/kg加伊匹单抗3 mg/kg 3 4，然后接受纳武单抗3 mg/kg 3 4。每2周一次，每次1 kg，直至疾病进展或出现不可接受的毒性，同时遵循既定的AE管理指南。分析了所有治疗相关的不良事件，选择（免疫相关）不良事件，发病和解决的时间，使用免疫调节剂及其对outcome.ResultsAmong 448例患者，随访的中位持续时间为13.2个月。55.5%的患者发生治疗相关3/4级AE; 35.7%的患者发生导致停药的治疗相关AE。最常见的任何级别的治疗相关选择AE为皮肤（64.3%）和GI（46.7%）以及3/4级、肝脏（17.0%）和GI（16.3%）; 30.1%的患者在一个以上器官类别中发生了2 - 4级选择AE。至3/4级治疗相关选定AE发作的中位时间范围为3.1（皮肤）至16.3（肾脏）周，排除内分泌AE后，至从发作消退的中位时间范围为1.9（肾脏）至4.5（肺部）周，使用免疫调节剂时消退率为79%至100%。四（，1%）的研究死亡归因于therapeutic.ConclusionFrequency 3/4级治疗相关的不良事件是较高的nivolumab加ipilimumab和发生早于历史经验与任何一个代理单独，但分辨率是相似的。(C)2017年美国临床肿瘤学会
PurposeThe addition of nivolumab (anti-programmed death-1 antibody) to ipilimumab (anti-cytotoxic T-cell lymphocyte-associated 4 antibody) in patients with advanced melanoma improves antitumor response and progression-free survival but with a higher frequency of adverse events (AEs). This cross-melanoma study describes the safety profile of the approved nivolumab plus ipilimumab regimen.MethodsThis retrospective safety review on data from three trials (phase I, II, and III) included patients with advanced melanoma who received at least one dose of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks 3 4 and then nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity while following established guidelines for AE management. Analyses were of all treatment-related AEs, select (immune-related) AEs, time to onset and resolution, and use of immune-modulating agents and their effects on outcome.ResultsAmong 448 patients, median duration of follow-up was 13.2 months. Treatment-related grade 3/4 AEs occurred in 55.5% of patients; 35.7% had treatment-related AEs that led to discontinuation. The most frequent treatment-related select AEs of any grade were skin (64.3%) and GI (46.7%) and of grade 3/4, hepatic (17.0%) and GI (16.3%); 30.1% developed a grade 2 to 4 select AE in more than one organ category. Median time to onset of grade 3/4 treatment-related select AEs ranged from 3.1 (skin) to 16.3 (renal) weeks, and with the exclusion of endocrine AEs, median time to resolution from onset ranged from 1.9 (renal) to 4.5 (pulmonary) weeks, with resolution rates between 79% and 100% while using immune-modulating agents. Four (, 1%) on-study deaths were attributed to therapy.ConclusionFrequency of grade 3/4 treatment-related AEs was higher with nivolumab plus ipilimumab and occurred earlier than historical experience with either agent alone, but resolution rates were similar. (C) 2017 by American Society of Clinical Oncology