PDF(Pubmed)
Abstract：
BACKGROUND: Antibody drug conjugates represent a promising class of antineoplastic agents comprised of a monoclonal antibody linked to a potent cytotoxic payload for targeted delivery of chemotherapy to tumors. Various antibody drug conjugates have demonstrated impressive efficacy in patients with metastatic urothelial carcinoma in clinical trials, leading to two FDA approved therapies and several other agents and combinations in clinical development.
METHODS: A comprehensive systematic review was undertaken utilizing the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Queried databases included Ovid MEDLINE, Ovid Embase, Web of Science Core Collection and Cochrane CENTRAL Trials. The search sought to identify prospective therapeutic clinical trials in humans with metastatic urothelial carcinoma with a single-arm or randomized controlled trial design investigating antibody drug conjugate-containing regimens.
RESULTS: The literature search yielded 4,929 non-duplicated articles, of which 30 manuscripts and conference abstracts were included, which derived from 15 clinical trials including 19 separate cohorts with efficacy outcome results. Eleven trials investigated ADC monotherapy, while two investigated combination regimens, and the remaining two studies were mixed. Five unique ADC targets were represented including Nectin-4, Trop-2, HER2, Tissue Factor, and SLITRK6. Twelve clinical trial cohorts required prior treatment (63%). Objective response rate was reported for all studies and ranged from 27-52% for ADC monotherapies and 34-75% for ADC plus anti-PD-1 agents. Time to event outcome reporting was highly variable.
CONCLUSIONS: In addition to enfortumab vedotin and sacituzumab govitecan, various HER2-targeted antibody drug conjugates and ADC-anti-PD-1 combination regimens have demonstrated efficacy in clinical trials and are poised for clinical advancement.
METHODS: A comprehensive systematic review was undertaken utilizing the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Queried databases included Ovid MEDLINE, Ovid Embase, Web of Science Core Collection and Cochrane CENTRAL Trials. The search sought to identify prospective therapeutic clinical trials in humans with metastatic urothelial carcinoma with a single-arm or randomized controlled trial design investigating antibody drug conjugate-containing regimens.
RESULTS: The literature search yielded 4,929 non-duplicated articles, of which 30 manuscripts and conference abstracts were included, which derived from 15 clinical trials including 19 separate cohorts with efficacy outcome results. Eleven trials investigated ADC monotherapy, while two investigated combination regimens, and the remaining two studies were mixed. Five unique ADC targets were represented including Nectin-4, Trop-2, HER2, Tissue Factor, and SLITRK6. Twelve clinical trial cohorts required prior treatment (63%). Objective response rate was reported for all studies and ranged from 27-52% for ADC monotherapies and 34-75% for ADC plus anti-PD-1 agents. Time to event outcome reporting was highly variable.
CONCLUSIONS: In addition to enfortumab vedotin and sacituzumab govitecan, various HER2-targeted antibody drug conjugates and ADC-anti-PD-1 combination regimens have demonstrated efficacy in clinical trials and are poised for clinical advancement.
摘要：
背景:抗体药物缀合物代表一类有希望的抗肿瘤剂,所述抗肿瘤剂由与有效的细胞毒性有效载荷连接的单克隆抗体组成,用于将化疗靶向递送至肿瘤。在临床试验中，各种抗体药物偶联物在转移性尿路上皮癌患者中表现出令人印象深刻的疗效，导致两种FDA批准的疗法和其他几种药物和组合在临床开发中。
方法：利用系统评价和荟萃分析（PRISMA）声明的首选报告项目的原则进行了全面的系统评价。查询的数据库包括OvidMEDLINE,OvidEmbase,WebofScience核心合集和CochraneCENTRAL试验。该搜索旨在通过单臂或随机对照试验设计研究含抗体药物缀合物的方案，确定转移性尿路上皮癌患者的前瞻性治疗性临床试验。
结果：文献检索产生了4,929篇非重复文章，其中包括30份手稿和会议摘要，来自15项临床试验，包括19个单独的具有疗效结局结果的队列。11项试验调查了ADC单一疗法，虽然两个研究的联合方案，其余两项研究混合在一起。五个独特的ADC靶标被代表，包括Nectin-4，Trop-2，HER2，组织因子，SLITRK612个临床试验队列需要事先治疗（63%）。所有研究均报告了客观反应率，ADC单一疗法为27-52％，ADC加抗PD-1药物为34-75％。至事件结果报告的时间差异很大。
结论：除了enfortumabvedotin和sacituzumabgovitecan，各种HER2靶向抗体药物偶联物和ADC-抗PD-1联合方案已在临床试验中证明了疗效,并为临床进展做好了准备.
方法：利用系统评价和荟萃分析（PRISMA）声明的首选报告项目的原则进行了全面的系统评价。查询的数据库包括OvidMEDLINE,OvidEmbase,WebofScience核心合集和CochraneCENTRAL试验。该搜索旨在通过单臂或随机对照试验设计研究含抗体药物缀合物的方案，确定转移性尿路上皮癌患者的前瞻性治疗性临床试验。
结果：文献检索产生了4,929篇非重复文章，其中包括30份手稿和会议摘要，来自15项临床试验，包括19个单独的具有疗效结局结果的队列。11项试验调查了ADC单一疗法，虽然两个研究的联合方案，其余两项研究混合在一起。五个独特的ADC靶标被代表，包括Nectin-4，Trop-2，HER2，组织因子，SLITRK612个临床试验队列需要事先治疗（63%）。所有研究均报告了客观反应率，ADC单一疗法为27-52％，ADC加抗PD-1药物为34-75％。至事件结果报告的时间差异很大。
结论：除了enfortumabvedotin和sacituzumabgovitecan，各种HER2靶向抗体药物偶联物和ADC-抗PD-1联合方案已在临床试验中证明了疗效,并为临床进展做好了准备.
