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Abstract：
BACKGROUND: Several immuno-oncology (IO) agents targeting programmed death-1 or programmed death-ligand 1 (PD-1/L1) are approved second-line therapy options for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) previously treated with platinum-based chemotherapy or first-line options in patients ineligible for cisplatin whose tumors express PD-L1 or for any platinum-based chemotherapy regardless of PD-L1 expression levels. However, literature on the epidemiology of la/mUC is limited, and real-world treatment patterns are not well established, especially with respect to therapies used following IO. OBJECTIVES: To (a) report the epidemiology of urothelial carcinoma (UC) and la/mUC; (b) identify and summarize the published literature on la/mUC treatment patterns, including IO and post-IO treatment; and (c) identify evidence gaps. METHODS: A systematic literature review was conducted using Cochrane dual-reviewer methodology and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Literature databases and selected congress abstracts (2017-2018) were searched for retrospective studies published January 2013-August 2018 in English reporting epidemiological and treatment data (all lines of therapy) for adult patients with la/mUC. RESULTS: Among 6,584 database references and 1,832 congress abstracts screened, 45 publications (29 manuscripts, 1 poster, 15 abstracts; reporting 37 unique studies) were retained. All studies related to treatment patterns, and the majority were from the United States (n = 17), Japan (n = 8), and the United Kingdom (n = 5). Epidemiological data were not identified among the searches thus online registries were leveraged. Among the identified publications, 21 (20 unique) reported on cisplatin versus non-cisplatin regimens, 14 (8 unique) on IO, and 9 (7 unique) on vinflunine. Cisplatin use varied both within and among countries (ranging from 18.4% in 1 U.S. study to 87.9% in 1 Japanese study). The use of IO was higher in later lines of therapy, ranging from 1.4% to 7.9% as first-line therapy to 57.8% as second-line and 64.4% as third-line therapy. Among studies reporting IO discontinuation rates, 41.4%-71% of patients were reported to discontinue IO across the studies, and the median time to discontinuation ranged from 2.7 to 5.8 months. Only 25%-35.5% of patients received subsequent therapy following IO discontinuation; post-IO treatments varied widely. CONCLUSIONS: Additional published data on the country-specific epidemiology of UC and la/mUC are needed, including rates of progression from early-stage disease to la/mUC. There was large variation in treatment rates, particularly cisplatin use, within and across countries. The few published real-world IO studies reported high levels of discontinuation with only a small percentage of patients receiving subsequent therapy. As IO therapies continue to be granted regulatory approval in countries outside the United States and novel therapies gain approval in the post-IO setting, the treatment paradigm for patients with la/mUC is shifting, and future studies with more recent data will be required. DISCLOSURES: This study was funded by Astellas/Seagen. Hepp is an employee of and owns stock in Seagen. Shah was a contractor for Astellas Pharma at the time of the study and owns stock in Pfizer. Smoyer is an employee and shareholder of Envision Pharma Group, paid consultants to Seagen. Vadagam was an employee of Envision Pharma Group, paid consultants to Seagen, at the time of the study. Parts of these data have been presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2019 Annual Meeting; May 18-22, 2019; New Orleans, LA.
摘要：
背景：针对程序性死亡-1或程序性死亡-配体1（PD-1/L1）的几种免疫肿瘤学（IO）药物已被批准用于局部晚期或转移性尿路上皮癌（la/mUC）患者的二线治疗方案，先前接受铂类化疗的患者或一线治疗的患者不符合顺铂（其肿瘤表达PD-L1）或不考虑PD-L1表达水平的任何铂类化疗的患者。然而,关于la/mUC流行病学的文献有限，现实世界的治疗模式并不完善，特别是关于IO后使用的疗法。目的：（a）报告尿路上皮癌（UC）和la/mUC的流行病学；（b）确定并总结已发表的关于la/mUC治疗模式的文献，包括IO和IO后治疗；以及(c)确定证据差距。方法：使用Cochrane双重审查方法和系统评价和荟萃分析方案的首选报告项目进行系统文献综述。检索了文献数据库和部分国会摘要（2017-2018），以英语报告的流行病学和治疗数据（所有治疗路线）为成年la/mUC患者发布的2013年1月至2018年8月的回顾性研究。结果：在6,584份数据库参考文献和1,832份大会摘要中，45种出版物(29份手稿,1张海报,15份摘要；报告37项独特研究)被保留。所有与治疗模式有关的研究，大多数来自美国（n=17），日本（n=8），和英国（n=5）。在搜索中没有确定流行病学数据，因此利用了在线注册表。在确定的出版物中，21例(20例)报道顺铂与非顺铂方案，在IO上有14个（8个唯一），和9（7个独特的）在vinflunine。顺铂的使用在国家内部和国家之间都有所不同（从1项美国研究中的18.4％到1项日本研究中的87.9％）。在后期的治疗中，IO的使用更高，一线治疗占1.4%至7.9%，二线治疗占57.8%，三线治疗占64.4%。在报告IO中止率的研究中，在整个研究中，41.4%-71%的患者被报告停止IO，停药时间中位数为2.7至5.8个月.只有25％-35.5％的患者在IO停药后接受了后续治疗；IO后治疗差异很大。结论：需要有关UC和la/mUC的国家特定流行病学的其他已发表数据，包括从早期疾病到la/mUC的进展率。治疗率差异很大，特别是使用顺铂，在国家内部和国家之间。少数已发表的真实世界IO研究报告了高水平的停药，只有一小部分患者接受后续治疗。随着IO疗法继续在美国以外的国家获得监管批准，并且新型疗法在IO后设置中获得批准，la/mUC患者的治疗模式正在发生变化，未来将需要更多最新数据的研究。披露：本研究由Astellas/Seagen资助。Hepp是Seagen的员工，并拥有Seagen的股票。Shah在研究时是AstellasPharma的承包商，并拥有辉瑞的股票。Smoyer是EnvisionPharmaGroup的员工和股东，给Seagen的顾问.Vadagam是EnvisionPharmaGroup的员工，Seagen的付费顾问,在研究的时候。这些数据的一部分已在国际药物经济学和结果研究学会（ISPOR）2019年年会上提出；2019年5月18日至22日；新奥尔良，LA.
