Horn T, Krege S, Retz M
Urologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstraße 22, 81675, München, Deutschland.
Abteilung für Urologie, Kinderurologie und Urologische Onkologie, Klinikum Essen-Mitte, Henricistraße 92, 45136, Essen, Deutschland.
Urologe A. 2018 Jun;57(6):686-692. doi: 10.1007/s00120-018-0626-2.
In November 2016, the results of a phase III clinical trial with the protein cell death (PD)-1 inhibitor pembrolizumab for second-line treatment of metastatic urothelial carcinoma were published and showed an overall survival benefit in comparison with conventional chemotherapy with vinflunine, docetaxel, or paclitaxel. In a similar trial the PD-L1 antibody atezolizumab showed no significant benefit in comparison to chemotherapy in the subgroup of PD-L1-positive patients and, thus, missed its primary endpoint. For other PD-1/PD-L1 directed substances, large phase I/II trials reported data concerning response rates and overall survival. This substance class will most likely become the new treatment standard in second-line treatment of metastatic urothelial cancer. Currently, PD-1/PD-L1 inhibitors are also being tested within randomized phase III trials for first-line treatment using different approaches either as a monotherapy or a combination with conventional chemotherapy or cytotoxic T‑lymphocyte-associated protein (CTLA)-4 inhibitors. Whereas data from single-arm phase II clinical trials have already been published, preliminary phase III data are expected in 2018.
2016年11月，一项关于蛋白细胞死亡（PD）-1抑制剂派姆单抗用于转移性尿路上皮癌二线治疗的III期临床试验结果发表，显示与使用长春氟宁、多西他赛或紫杉醇的传统化疗相比，具有总生存获益。在一项类似试验中，PD-L1抗体阿特珠单抗在PD-L1阳性患者亚组中与化疗相比未显示出显著获益，因此未达到其主要终点。对于其他PD-1/PD-L1导向药物，大型I/II期试验报告了有关缓解率和总生存的数据。这类药物很可能成为转移性尿路上皮癌二线治疗的新标准。目前，PD-1/PD-L1抑制剂也正在随机III期试验中进行一线治疗测试，采用不同方法，要么作为单药治疗，要么与传统化疗或细胞毒性T淋巴细胞相关蛋白（CTLA）-4抑制剂联合使用。虽然单臂II期临床试验的数据已经发表，但预计2018年将公布III期初步数据。
