Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials.
Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials.
复制标题
DOI：
10.18632/oncotarget.13315
复制
发表时间：
2017-01-31
期刊：
影响因子：
--
通讯作者：
Giles FJ
中科院分区：
文献类型：
--
作者：
Costa R;Carneiro BA;Agulnik M;Rademaker AW;Pai SG;Villaflor VM;Cristofanilli M;Sosman JA;Giles FJ
Nivolumab和pembrolizumab是针对程序性死亡受体-1 （PD-1）的抗体，与不同的免疫相关不良反应（ae）相关。这项随机临床试验的荟萃分析旨在总结目前关于这些药物毒性概况的知识。PubMed检索于2016年2月进行。随机试验需要至少有一个研究组由纳武单抗或派姆单抗单药治疗组成，而对照组不含抗pd -1治疗。数据分析采用随机效应风险比荟萃分析。使用Q和I2统计分析各研究的异质性。我们的荟萃分析纳入了9项随机试验和5353名患者。有证据表明研究之间存在显著的异质性。治疗相关的所有级别ae和3/4级ae的总相对危险度（RR）分别为0.88 （95% CI 0.81-0.95；P=0.002）和0.39 (95% CI 0.29-0.53； P<0.001)，分别倾向于抗pd -1治疗和标准护理方法。治疗相关死亡的RR为0.45 （95% CI 0.19-1.09； P=0.076）。接受PD-1抑制剂治疗的患者甲状腺功能亢进[RR为3.44 (95% CI 1.98-5.99； P<0.001)]和甲状腺功能减退[RR为6.79 (95% CI 3.10-14.84； P<0.001)]的风险增加。所有级别的瘙痒和白癜风在这些患者中也更为常见。肺炎和垂体炎的绝对风险分别为2.65%和0.47%。经批准的PD-1抑制剂耐受性良好，与严重治疗相关不良反应的风险显著降低以及甲状腺功能障碍、瘙痒和白癜风的风险增加相关。
Nivolumab and pembrolizumab are antibodies against the programmed-death-receptor- 1 (PD-1) which are associated with distinct immune related adverse effects (AEs). This meta-analysis of randomized clinical trials aims to summarize current knowledge regarding the toxicity profile of these agents. PubMed search was conducted in February of 2016. The randomized trials needed to have at least one of the study arms consisting of nivolumab or pembrolizumab monotherapy and a control arm containing no anti-PD-1 therapy. Data were analyzed using random effects meta-analysis for risk ratios. Heterogeneity across studies was analyzed using Q and I2 statistics. Nine randomized trials and 5,353 patients were included in our meta-analysis. There was evidence of significant heterogeneity between studies. The pooled relative risk (RR) for treatment-related all grade AEs and grade 3/4 AEs was 0.88 (95% CI 0.81-0.95;P=0.002) and 0.39 (95% CI 0.29-0.53; P<0.001) respectively favoring anti-PD-1 therapy versus standard of care approach. The RR of treatment-related death was 0.45 (95% CI 0.19-1.09; P=0.076). Patients treated with PD-1 inhibitors had an increased risk of hyperthyroidism [RR of 3.44 (95% CI 1.98-5.99; P<0.001)] and hypothyroidism [RR of 6.79 (95% CI 3.10-14.84; P<0.001)]. All grade pruritus and vitiligo were also more common among these patients. The pooled absolute risks of pneumonitis and hypophysitis were 2.65% and 0.47% respectively. Approved PD-1 inhibitors are well tolerated, associated with significant low risk of severe treatment-related AEs and increased risk of thyroid dysfunction, pruritus, and vitiligo.