Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma
Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma
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DOI：
10.1200/jco.2015.66.1389
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发表时间：
2017-03-01
影响因子：
45.3
通讯作者：
Robert, Caroline
中科院分区：
文献类型：
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作者：
Weber, Jeffrey S.;Hodi, F. Stephen;Robert, Caroline
PurposeWe进行了一项回顾性分析，以评估nivolumab单药治疗晚期黑色素瘤患者的安全性，并描述了使用已建立的安全性guidelines.Patients and MethodsSafety数据汇总来自四项研究，包括两项III期试验，患者每2周接受nivolumab 3 mg/kg一次。我们评估了治疗相关AE的发生率、至发作时间和选定AE的消退（具有潜在免疫病因的患者），以及选择的AE和抑制性免疫调节剂（IM）对抗肿瘤疗效的影响。（95% CI，67%-75%）发生任何级别的治疗相关AE（最常见的是疲劳[25%]、瘙痒[17%]、腹泻[13%]和皮疹[13%]），10%（95% CI，8%-13%）发生3 - 4级治疗相关AE。未报告药物相关死亡。选定AE（发生于49%的患者）最常见的是皮肤相关、GI、内分泌和肝脏; 4%的患者发生3 - 4级选定AE。至特定AE发生的中位时间范围为5周（皮肤AE）至15周（肾脏AE）。约24%的患者接受全身IM治疗，以管理选定的AE，大多数病例已消退。调整给药次数后，发生任何级别治疗相关选定AE的患者的客观缓解率（ORR）显著高于未发生AE的患者。ORR是相似的患者谁没有接受全身IMs. ConclusionTreatment相关的不良事件与nivolumab单药治疗主要是低级别，并与既定的安全性指南解决。使用IM不影响ORR，尽管任何级别的治疗相关选择AE均与较高的ORR相关，但无无进展生存期获益。(C)2016年美国临床肿瘤学会
PurposeWe conducted a retrospective analysis to assess the safety profile of nivolumab monotherapy in patients with advanced melanoma and describe the management of adverse events (AEs) using established safety guidelines.Patients and MethodsSafety data were pooled from four studies, including two phase III trials, with patients who received nivolumab 3 mg/kg once every 2 weeks. We evaluated rate of treatment-related AEs, time to onset and resolution of select AEs (those with potential immunologic etiology), and impact of select AEs and suppressive immune-modulating agents (IMs) on antitumor efficacy.ResultsAmong 576 patients, 71% (95% CI, 67% to 75%) experienced any-grade treatment-related AEs (most commonly fatigue [25%], pruritus [17%], diarrhea [13%], and rash [13%]), and 10% (95% CI, 8% to 13%) experienced grade 3 to 4 treatment-related AEs. No drug-related deaths were reported. Select AEs (occurring in 49% of patients) were most frequently skin related, GI, endocrine, and hepatic; grade 3 to 4 select AEs occurred in 4% of patients. Median time to onset of select AEs ranged from 5 weeks for skin to 15 weeks for renal AEs. Approximately 24% of patients received systemic IMs to manage select AEs, which in most cases resolved. Adjusting for number of doses, objective response rate (ORR) was significantly higher in patients who experienced treatment-related select AEs of any grade compared with those who did not. ORRs were similar in patients who did and patients who did not receive systemic IMs.ConclusionTreatment-related AEs with nivolumab monotherapy were primarily low grade, and most resolved with established safety guidelines. Use of IMs did not affect ORR, although treatment-related select AEs of any grade were associated with higher ORR, but no progression-free survival benefit. (C) 2016 by American Society of Clinical Oncology