Dr Bedke on Advice for Using Enfortumab Vedotin/Pembrolizumab in Previously Untreated Advanced Urothelial Carcinoma

“The efficacy [data], which are so strong and have such an enormous delta [in favor of] enfortumab vedotin plus pembrolizumab in this first-line setting, justify the use, more or less, in all patients.”

Jens Bedke, MD, a member of the Department of Urology at the Eva Mayr-Stihl Cancer Center in German, and a professor of urology at the University of Tübingen, discussed practical considerations for incorporating enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) into the frontline treatment paradigm for patients with previously untreated advanced urothelial carcinoma.

Data from the phase 3 EV-302 trial (NCT04223856) demonstrated that enfortumab vedotin plus pembrolizumab significantly improved progression-free survival, overall survival, and objective response rates compared with platinum-based chemotherapy, establishing the combination as the preferred standard of care for eligible patients. According to Bedke, the benefit of enfortumab vedotin plus pembrolizumab was consistent across all evaluated subgroups, regardless of metastatic site or primary tumor location, including lymph node, liver, upper tract, and lower tract. Therefore, disease distribution should not guide patient selection for enfortumab vedotin plus pembrolizumab, he said. Instead, enfortumab vedotin plus pembrolizumab should be considered broadly in the first-line setting given its efficacy advantage over platinum regimens, he explained. Bedke noted that many oncologists are already familiar with both agents individually: pembrolizumab from its use as a checkpoint inhibitor and enfortumab vedotin from its approved role as monotherapy in later-line settings. The combination leverages this prior experience but requires awareness of overlapping and unique toxicities.

Key adverse effects associated with enfortumab vedotin plus pembrolizumab that oncologists should be aware of include dermatologic reactions, peripheral neuropathy with both sensory and motor components, hyperglycemia, and ocular toxicities, he stated. Although enfortumab vedotin plus pembrolizumab is appropriate for most patients with advanced urothelial carcinoma, Bedke advised caution in select populations. Contraindications include prior organ transplantation and severe immune-related disorders that preclude the safe administration of checkpoint inhibitors, he added. Outside of these scenarios, enfortumab vedotin plus pembrolizumab is endorsed by international guidelines as a preferred first-line regimen, he concluded.