Administration of Enfortumab Vedotin after Immune-Checkpoint Inhibitor and the Prognosis in Japanese Metastatic Urothelial Carcinoma: A Large Database Study on Enfortumab Vedotin in Metastatic Urothelial Carcinoma

SIMPLE SUMMARY: Enfortumab vedotin, a targeted therapy for advanced urothelial carcinoma, has shown efficacy, especially in those treated with platinum-based chemotherapy and immune-checkpoint inhibitors. The EV-301 phase III trial reported enhanced overall survival and response rates than conventional chemotherapy. However, its effectiveness in Japanese patients needs further real-world validation. Analyzing 6007 urothelial cancer patients treated with pembrolizumab, 563 subsequently received enfortumab vedotin, while 443 switched to docetaxel or paclitaxel. Results indicated the enfortumab vedotin group had an extended overall survival compared to the paclitaxel/docetaxel group (p = 0.013, HR: 0.71). Conclusively, enfortumab vedotin offers Japanese patients better overall survival prospects after pembrolizumab treatment than docetaxel or paclitaxel. ABSTRACT: Background: Enfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who have previously received platinum-based chemotherapy and an immune-checkpoint inhibitor. The EV-301 phase III trial demonstrated significantly improved overall survival and response rates compared to standard chemotherapy. However, more data, especially from larger real-world studies, are needed to further assess its effectiveness in Japanese patients. Methods: A total of 6007 urothelial cancer patients inducted with pembrolizumab as a second-line treatment were analyzed. Among them, 563 patients received enfortumab vedotin after pembrolizumab, while 443 patients received docetaxel or paclitaxel after pembrolizumab, and all were included in the study for efficacy as a life prolonging agent. Results: The enfortumab vedotin group showed a longer overall survival than the paclitaxel/docetaxel group (p = 0.013, HR: 0.71). In multivariate analysis, enfortumab vedotin induction was the independent risk factor for overall survival (p = 0.013, HR: 0.70). There were no significant differences in cancer-specific survival. Conclusions: Enfortumab vedotin prolonged the overall survival for Japanese advanced or metastatic urothelial carcinoma patients compared to paclitaxel or docetaxel after pembrolizumab treatment.