Current Systemic Treatment Options in Metastatic Urothelial Carcinoma after Progression on Checkpoint Inhibition Therapy—A Systemic Review Combined with Single-Group Meta-Analysis of Three Studies Testing Enfortumab Vedotin

SIMPLE SUMMARY: Currently, little is known about what therapeutic options exist for the treatment of metastatic urothelial carcinoma (mUC) after a therapy with checkpoint inhibitors (CPI). In the context of this systemic review, five therapy regimens tested in the post-CPI setting with adequate data were identified: Chemotherapy (CT), Ramucirumab plus Docetaxel, Erdafitinib (Erd), Enfortumab vedotin (EV), and Sacituzumab govitecan (SG). Most data were available on EV, and the results of three studies testing the agent were combined via single-group meta-analysis. For EV, the objective response rate was 42.1% compared to 17.9% for CT in a similar setting. EV was also ahead in progression-free survival (5.9 months with EV vs. 3.7 months with CT) and overall survival (12.8 months with EV vs. 9.0 months with CT). Further research is needed on the question of which patients’ subcollectives particularly benefit from which therapeutic approach. ABSTRACT: Background: In the first and second-line therapy of metastatic urothelial carcinoma (mUC), checkpoint inhibitors (CPI) such as Pembrolizumab and Atezolizumab have been widely implemented. Little is currently known about what therapeutic options are effective after therapy with CPI. This article presents a systemic review of current treatment options in this setting. Methods: From August 2020 to 15 April 2021, a literature search was performed through the PubMed/Medline. Subsequently, a single-group meta-analysis of three studies testing Enfortumab vedotin (EV) was conducted. Results: Five therapy regimens tested in the post-CPI setting with adequate data were identified: Chemotherapy (CT), Ramucirumab plus Docetaxel, Erdafitinib (Erd), EV, and Sacituzumab govitecan (SG). In n = 74 + 125 + 288 patients, the single-group meta-analysis showed an objective response rate of 42.1% for EV compared to 17.9% for CT in a similar setting. EV was also ahead in progression free survival (5.9 months with EV vs. 3.7 months with CT) and overall survival (12.8 months with EV vs. 9.0 months with CT). Conclusion: Most data are currently available for EV. Further research is needed on the question of which patients’ subcollectives particularly benefit from which therapeutic approach.