Second-line therapy for metastatic urothelial carcinoma: Defining the best treatment option among immunotherapy, chemotherapy, and antiangiogenic targeted therapies. A systematic review and meta-analysis

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.