Grunewald Camilla Marisa, Hiester Andreas, Niegisch Günter
Heinrich-Heine-Universität Düsseldorf, Medizinische Fakultät, Klinik für Urologie.
Aktuelle Urol. 2020 Aug;51(4):371-376. doi: 10.1055/a-1136-9850. Epub 2020 Apr 7.
The increasing knowledge of the influence of the immune system on tumour development and progression has fundamentally changed our understanding of tumour biology in recent years. While the available treatment options for patients with metastatic urothelial carcinoma of the urinary bladder have hardly improved over decades, the advent of immune checkpoint inhibitors has caused major changes in the corresponding treatment landscape.Although cisplatin-based combination therapies remain the main element, additional effective treatment options now exist with the PD-(L)-1 inhibitors atezolizumab, pembrolizumab and nivolumab, which have been approved in Europe. A remarkable long-term response is balanced by the occurrence of occasionally severe immune-mediated side effects and an overall low response rate of approximately 25 %. A large number of current clinical trials therefore address possible combinatory approaches in order to make optimal use of possible synergisms and additive effects of the substances available to date, taking into account an acceptable side effect profile. In addition, many new therapeutic approaches are also being tested in clinical trials. In this context, developments in the field of antibody-drug conjugates and FGFR inhibitors with regards to the very recent FDA approvals are particularly noteworthy.The present review provides an overview of currently available treatment options in metastatic urothelial carcinoma of the bladder and especially focuses on future therapeutic approaches based on current clinical trials.
近年来,免疫系统对肿瘤发生和进展影响的认知不断增加,从根本上改变了我们对肿瘤生物学的理解。几十年来,转移性膀胱尿路上皮癌患者可用的治疗选择几乎没有改善,但免疫检查点抑制剂的出现使相应的治疗格局发生了重大变化。尽管基于顺铂的联合疗法仍然是主要治疗手段,但目前欧洲已批准的PD-(L)-1抑制剂阿特珠单抗、帕博利珠单抗和纳武利尤单抗提供了额外的有效治疗选择。显著的长期缓解与偶尔出现的严重免疫介导副作用以及约25%的总体低缓解率相平衡。因此,大量当前的临床试验探讨了可能的联合治疗方法,以便在考虑可接受的副作用特征的情况下,充分利用现有药物可能的协同作用和累加效应。此外,许多新的治疗方法也正在临床试验中进行测试。在此背景下,抗体药物偶联物和FGFR抑制剂领域在近期获得美国食品药品监督管理局(FDA)批准方面的进展尤其值得关注。本综述概述了目前转移性膀胱尿路上皮癌可用的治疗选择,并特别关注基于当前临床试验的未来治疗方法。