Combination treatment with Enfortumab vedotin (EV), an antibody drug conjugate targeting Nectin-4 with a monomethyl auristatin E (MMAE) payload, and pembrolizumab, a programmed death 1 (PD-1) inhibitor, has become the new standard of care for previously untreated locally advanced or metastatic urothelial carcinoma. In the recently published phase III study, EV-302, EV and pembrolizumab demonstrated improved outcomes compared to platinum-based chemotherapy, including objective response rate, progression free survival, and an unprecedented median overall survival of 33.8 months (versus 15.9 months; hazard ratio for death 0.51; 95% confidence interval 0.43-0.61; p < 0.00001). We reviewed the mechanism of action, clinical efficacy, exploratory biomarkers, and safety profile of EV and pembrolizumab as monotherapies and combination in urothelial cancer.
What is this article about?This review provides information about the use of a new combination of two drugs- enfortumab vedotin (EV) and pembrolizumab, in the treatment of metastatic urothelial cancer.What have studies shown?Both EV and pembrolizumab have previously individually shown to be effective in bladder cancer after other treatments have failed. In a large study including 886 patients, the new combination of EV and pembrolizumab was compared to the standard chemotherapy as the first treatment in patients with bladder cancer. Patients treated with EV and pembrolizumab lived longer and had a longer time without cancer progression compared to patients treated with chemotherapy. Patients treated with EV and pembrolizumab were more likely to have meaningful tumor shrinkage: in 30.4% the tumors were no longer detected on imaging scans compared to 14.5% with chemotherapy. Serious side effects can occur with the new treatment including rash, nerve damage, high blood sugar, and lung inflammation.What conclusions can be made from these studies?The combination of enfortumab vedotin and pembrolizumab is the new recommended treatment for locally advanced and metastatic urothelial cancer.
Future oncology (London, England). 2025 Mar 25 [Epub ahead of print]
Michal Sternschuss, Jonathan E Rosenberg
Genitourinary Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.