EU okays new first-line treatment for advanced urothelial cancer

The European Commission has granted marketing authorisation for antibody-drug conjugate (ADC) Padcev (enfortumab vedotin) in combination with PD-1 inhibitor Keytruda (pembrolizumab) for urothelial cancer. It is approved for the first-line treatment of adult patients with unresectable or metastatic cancer, who are eligible for platinum-containing chemotherapy. The approval is based on results from the Phase III EV-302 clinical trial (KEYNOTE-A39) which showed that enfortumab vedotin in combination with pembrolizumab nearly doubled median overall survival (OS) and significantly extended progression-free survival (PFS) compared to platinum-containing chemotherapy. Dr Thomas Powles, Barts Cancer Institute Biomedical Research Centre, UK, said: “Having an effective new first-line treatment for advanced urothelial cancer is opening a long-awaited new chapter in the management of this usually fatal disease. The impressive effects of the treatment combination were clearly seen during the Phase III clinical trial programme, with enfortumab vedotin in combination with pembrolizumab significantly extending overall survival and progression-free survival compared to platinum-containing chemotherapy. I look forward to seeing the treatment combination implemented as a first-line regimen in the clinical setting.” The Phase III EV-302 clinical trial Enfortumab vedotin-ejfv was co-developed by Pfizer and Astellas. It is directed to Nectin-4, a protein highly expressed in bladder cancer. Nonclinical data suggest the treatment’s anticancer activity of is due to its binding to Nectin-4-expressing cells, followed by the internalisation and release of the anti-tumour agent monomethyl auristatin E into the cell. The combination treatment was approved by the US Food and Drug Administration (FDA) in December 2023. Ahsan Arozullah, Senior Vice President and Head of Oncology Development, Astellas, commented: “This approval is testament to our ongoing partnership with clinical trial investigators, study participants and their families, and the broader bladder cancer community. We look forward to patients across the European Union gaining benefit from this combination early in their treatment journey.” Results of the Phase III EV-302 clinical trial showed that the treatment combination resulted in a median OS of 31.5 months compared to 16.1 months with platinum-containing chemotherapy. The median PFS of 12.5 months with the combination compared to 6.3 months with chemotherapy. Diana Spencer, Senior Digital Content Editor, DDW