Evidence Synthesis, Modeling & Communication, Evidera, London, UK.
AstraZeneca, Gaithersburg, MD, USA.
Cancer Treat Rev. 2020 Sep;89:102072. doi: 10.1016/j.ctrv.2020.102072. Epub 2020 Jul 22.
Patients with advanced urothelial carcinoma (UC) have poor outcomes, with 5-year survival rates of <5% for those with metastatic, stage IV disease. We have reviewed current treatment paradigms and emerging treatment options for these patients.
The websites of seven national or international organizations were searched for metastatic UC treatment guidelines. Systematic literature reviews were conducted to identify evidence from randomized controlled trials (RCTs) of chemotherapy for patients with previously untreated, unresectable, stage IV UC. Searches included congress databases and articles published between 1990 and 2018. In order to align with the latest treatment paradigms in first-line advanced UC, a focused literature search was conducted to identify evidence supporting immuno-oncology (IO) agents.
For advanced UC, guidelines universally recommend cisplatin-based chemotherapy as first-line treatment for eligible patients and carboplatin-based regimens for those unfit to receive cisplatin. Despite the evaluation of a number of different cytotoxic regimens over the years, including triplet combinations, survival outcomes have not improved markedly with chemotherapy. Median overall survival with standard of care chemotherapy is ~13 months. Based on the results of single-arm, phase II studies, recent treatment guidelines have included atezolizumab (anti-PD-L1) and pembrolizumab (anti-PD-1) as first-line options for cisplatin-ineligible patients whose tumors express high levels of PD-L1. However, emerging evidence from RCTs of IO agents, including both cisplatin-eligible and cisplatin-ineligible patients, suggest that survival times exceeding 20 months are possible.
After having reached a plateau with chemotherapy, the treatment landscape for advanced UC is evolving. Survival outcomes for patients with advanced UC are improving with treatment modalities involving IO agents.
患有晚期尿路上皮癌（UC）的患者预后较差，转移性 IV 期疾病患者的 5 年生存率<5%。我们回顾了这些患者的当前治疗模式和新出现的治疗选择。
搜索了七个国家或国际组织的网站，以获取转移性 UC 治疗指南。进行了系统的文献回顾，以确定对未经治疗、不可切除的 IV 期 UC 患者进行化疗的随机对照试验（RCT）的证据。搜索包括会议数据库和 1990 年至 2018 年期间发表的文章。为了与一线晚期 UC 的最新治疗模式保持一致，还进行了针对性的文献检索，以确定支持免疫肿瘤学（IO）药物的证据。
对于晚期 UC，指南普遍建议将基于顺铂的化疗作为有条件患者的一线治疗选择，将基于卡铂的方案用于不适合接受顺铂的患者。尽管多年来评估了许多不同的细胞毒性方案，包括三联方案，但化疗的生存结果并没有明显改善。标准护理化疗的中位总生存期约为 13 个月。基于单臂、II 期研究的结果，最近的治疗指南已将阿替利珠单抗（抗 PD-L1）和帕博利珠单抗（抗 PD-1）纳入标准护理，适用于肿瘤高表达 PD-L1 的不适合接受顺铂的患者的一线治疗选择。然而，来自 IO 药物 RCT 的新出现的证据，包括适合和不适合接受顺铂的患者，表明超过 20 个月的生存时间是可能的。
在化疗达到平台期后，晚期 UC 的治疗格局正在发生变化。免疫肿瘤学药物治疗模式的出现正在改善晚期 UC 患者的生存结果。
