Dr Bedke on the Safety Profile of Enfortumab Vedotin/Pembrolizumab in Previously Untreated Advanced Urothelial Carcinoma

“We must be careful in managing these patients and be aware of the specific [adverse] effect profile. It’s not that a specific subgroup [was more or less prevalent] than the other, and this is a good signal for the clinical setting.”

Jens Bedke, MD, a senior consultant in the Department of Urology and Transplantation at the Eva Mayr-Stihl Cancer Center, discussed the safety profile of enfortumab vedotin (Padcev) plus pembrolizumab (Keytruda) compared with platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma. He emphasized that, in the intent-to-treat population, the incidence of grade 3 or 4 adverse effects [AEs] was numerically similar between the 2 treatment groups. However, the toxicity profile differed meaningfully, with the enfortumab vedotin–pembrolizumab regimen associated with distinct adverse effects of special clinical interest compared with chemotherapy.

Platinum-based chemotherapy was primarily associated with hematologic toxicities, which were notably absent with enfortumab vedotin/pembrolizumab, Bedke continued. Instead, patients receiving enfortumab vedotin/pembrolizumab experienced dermatologic toxicities, including rash and other skin disorders, as well as sensory and motor polyneuropathy, he explained. Additionally, ocular AEs such as blurred vision and other eye disorders were observed, with cases spanning multiple subcategories, he said.

Bedke noted that these treatment-related AEs require recognition and proactive management in the clinical setting. The distinct safety profile of enfortumab vedotin/pembrolizumab underscores the need for early detection and intervention for skin, neurologic, and ocular toxicities, which could differ in both onset and clinical management from the hematologic events typically seen with chemotherapy, he added.

Importantly, subgroup analyses showed no significant differences in the type or frequency of these AEs across clinical subgroups, including patients with liver metastases compared with those with only lymph node–only disease, Bedke asserted. This suggests that the safety profile of enfortumab vedotin/pembrolizumab is consistent regardless of disease burden or metastatic pattern, offering reassurance for its applicability across a broad range of patient presentations, he explained.

Bedke stressed that although the overall severity of AEs is comparable to chemotherapy, clinicians should anticipate and monitor for the unique toxicities associated with enfortumab vedotin/pembrolizumab.