Enfortumab Vedotin Combo Supersedes Other Advanced Bladder Cancer Options

In a conversation with CancerNetwork® at the 2025 ASCO Genitourinary Cancer Symposium, Thomas Powles, MBBS, MRCP, MD, described how updated findings from the phase 3 EV-302 trial (NCT04223856) may influence the standard of care for patients with previously untreated advanced or metastatic urothelial carcinoma. According to Powles, these results support enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) as an option that supersedes other treatment strategies in this patient population.

Powles, a professor of genitourinary oncology, lead for Solid Tumor Research, and director of Barts Cancer Institute at St. Bartholomew’s Hospital, Queen Mary University of London, in London, United Kingdom, highlighted the enfortumab vedotin combination as a preferred option over prior standards of care such as gemcitabine plus cisplatin. Additionally, he described a need to explore similar treatment regimens in earlier settings, which included assessing enfortumab vedotin–based combinations as neoadjuvant therapy.

Transcript:

Enfortumab vedotin plus pembrolizumab supersedes other approaches in this environment. I don’t think [gemcitabine/cisplatin] or [gemcitabine/carboplatin] with either nivolumab [Opdivo] or maintenance durvalumab [Imfinzi] have a major population where you would choose them instead. There are patients who are not fit enough for systemic therapy, of course, and there are [certain] patients who have contraindications to immune checkpoint inhibition [and may have] active arthritis on immunosuppressive therapy. But as a rule, this [combination] supersedes previous chemotherapy.

We still need to do better in urothelial cancer. We need to group these regimens earlier in the disease, where I believe it to be more curable. We need to look at the results of the perioperative trials in that space, and that’s going to be really exciting. There are neoadjuvant trials with [enfortumab vedotin plus pembrolizumab] and [enfortumab vedotin plus durvalumab and tremelimumab (Imjudo)]. I expect to see similar results. I hope what we might even do is be able to cure patients in the perioperative space without surgery. It’s a very exciting time in urothelial cancer.

Reference

Powles TB, Van der Heijden MS, Loriot Y, et al. EV-302: Updated analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). J Clin Oncol. 2025;43(suppl 5):664. doi:10.1200/JCO.2025.43.5_suppl.664