Ramucirumab as a second-line treatment for locally advanced or metastatic urothelial carcinoma: a meta-analysis of randomized clinical trials

Improvement of treatment outcomes in patients with locally advanced or metastatic urothelial carcinoma represents an important unmet need, since survival remains poor in patients who progressed after first-line treatment. The purpose of this study was to investigate the effects of ramucirumab, a human monoclonal antibody which binds to VEGFR-2, in the treatment of locally advanced or metastatic urothelial carcinoma. A literature search of PubMed and CENTRAL was conducted. Outcomes of interest were overall survival (OS), progression-free survival (PFS) and rate of adverse events. Time-to-event outcomes were combined using the generic inverse-variance method and presented as hazard ratio (HR) with 95% confidence intervals (95%CI), while dichotomous events were combined using the Mantel-Haenszel method and presented as odds ratio (OR) with 95%CI. All analyses were performed in RevMan 5.3. Literature search identified two randomized controlled trials. Addition of ramucirumab to docetaxel resulted in a statistically significant improvement in PFS (HR=0.55, 95%CI 0.31-0.96, p=0.030), while the difference was not significant for OS (HR=0.86, 95%CI 0.71-1.04, p=0.12). Subgroup analysis by sex, age (<65 and ≥65 years), baseline hemoglobin (<10 g/dL and ≥10 g/dL), presence of visceral metastases and presence of liver metastases did not identify a subgroup in which improvement in OS was present. The difference in treatment-related grade≥3 adverse events was not significant (OR=1.47, 95%CI 0.95-2.27, p=0.08). Ramucirumab in addition to docetaxel significantly improved PFS in patients with locally advanced or metastatic urothelial carcinoma. Future studies are necessary to identify a subset of patients who might have a significant improvement in OS.