UOC di Oncologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.
UOC di Oncologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Semin Oncol. 2019 Feb;46(1):65-72. doi: 10.1053/j.seminoncol.2019.01.001. Epub 2019 Jan 14.
There is no second-line standard of care universally accepted for platinum-refractory metastatic urothelial carcinoma. Immunotherapy and anti-VEGF(R) targeted therapies are 2 emerging strategies with promising though inconclusive results. We perform a systematic meta-analysis to assess the available options. We searched MEDLINE/PubMed, the Cochrane Library, and American society of clinical oncology (ASCO) Meeting abstracts to identify prospective studies. Data extraction was conduced according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The measured outcomes were overall survival (OS) and progression free survival (PFS). Seven randomized controlled trials were selected for final analysis, with a total of 2,451 evaluable patients. Chemotherapy with vinflunine did not reduce the risk of progression (HR = 1.11; 95%CI 0.78-1.57; P = .56) or death (HR = 0.97; 95%CI 0.70-1.34; P = .87) compared to taxanes. Immunotherapy with anti-PD-1/PD-L1 mAb improved OS over chemotherapy (HR = 0.81; 95% CI 0.71-0.92; P<.0009). The OS benefit of immunotherapy was retained when compared to taxanes, but not compared to vinflunine, although without a significant difference between the 2 subgroups (P = .30). A lack of PFS (HR = 0.73; P = .08) and OS (HR = 1.0; P = .99) benefit was observed with an anti-VEGF(R) plus chemotherapy compared to chemotherapy alone. No PFS (P = .14) or OS (P = .13) differences were detected when comparing anti-VEGF(R) ± chemotherapy and immunotherapy. Immunotherapy significantly improved OS compared to chemotherapy in metastatic urothelial carcinoma unselected for PD-L1 status. The addition of anti-VEGF(R) to chemotherapy did not provide any statistically significant benefit in terms of PFS or OS. Single agent taxanes or vinflunine can be considered given their similar efficacy but different toxicity profiles.
对于铂类耐药的转移性尿路上皮癌，目前尚无普遍接受的二线标准治疗方法。免疫疗法和抗血管内皮生长因子（VEGF）靶向治疗是 2 种新兴策略，具有有前途但不确定的结果。我们进行了系统的荟萃分析来评估现有选择。我们检索了 MEDLINE/PubMed、Cochrane 图书馆和美国临床肿瘤学会（ASCO）会议摘要，以确定前瞻性研究。根据系统评价和荟萃分析的首选报告项目（PRISMA）声明进行数据提取。测量结果是总生存期（OS）和无进展生存期（PFS）。最终分析选择了 7 项随机对照试验，共 2451 名可评估患者。与紫杉烷类药物相比，vinflunine 化疗并未降低进展风险（HR=1.11；95%CI 0.78-1.57；P=0.56）或死亡风险（HR=0.97；95%CI 0.70-1.34；P=0.87）。与化疗相比，抗 PD-1/PD-L1 mAb 免疫治疗改善了 OS（HR=0.81；95%CI 0.71-0.92；P<.0009）。与紫杉烷类药物相比，免疫治疗的 OS 获益得以保留，但与 vinflunine 相比则不然，尽管这 2 个亚组之间没有显著差异（P=0.30）。与单独化疗相比，抗 VEGF（R）联合化疗并未观察到 PFS（HR=0.73；P=0.08）和 OS（HR=1.0；P=0.99）获益。与免疫治疗相比，抗 VEGF（R）±化疗并未显示出 PFS（P=0.14）或 OS（P=0.13）差异。免疫治疗在未选择 PD-L1 状态的转移性尿路上皮癌中显著改善了 OS。与单独化疗相比，抗 VEGF（R）的添加并未在 PFS 或 OS 方面提供任何统计学上的显著获益。由于其相似的疗效和不同的毒性谱，单药紫杉烷类药物或 vinflunine 可被考虑使用。
