Dr Lee on Treatment Considerations for Enfortumab Vedotin Plus Pembrolizumab in Urothelial Cancer

John K. Lee, MD, PhD, assistant professor, medicine, University of California, San Francisco; director, Bladder Cancer Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses key considerations that may inform the use of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) in metastatic urothelial cancer.

On December 15, 2023, the FDA approved enfortumab vedotin in combination with pembrolizumab as frontline therapy for patients with metastatic urothelial cancer. The regulatory decision was based on results from the phase 3 EV-302 trial (NCT04223856), which demonstrated a survival benefit with the combination compared with standard chemotherapy.

Lee begins by emphasizing the importance of individualized treatment decisions for patients with metastatic urothelial cancer, as well as factoring in potential treatment-related toxicities. Although the combination of enfortumab vedotin and pembrolizumab has shown superior clinical efficacy, it also presents specific challenges, he notes. For example, the higher risk of developing hyperglycemia, especially in patients with uncontrolled diabetes, highlights the need for careful patient selection when considering the selection of this combination.

Notably, the median follow-up for EV-302 was approximately 17.2 months, which generates questions about the long-term durability of the combination, Lee explains. This is a key consideration when juxtaposed with the well-established efficacy of cisplatin-based chemotherapy plus immunotherapy, which support its use in patients with lymph node-only disease.

Moreover, the immune checkpoint inhibitor pembrolizumab may not be suitable for patients with a history of solid organ transplants or autoimmune disorders, Lee adds. For these patients, upfront cisplatin-based chemotherapy alone may be a safer and more appropriate choice, he suggests.

Although the combination of enfortumab vedotin plus pembrolizumab offers a highly effective new treatment option for patients with metastatic bladder cancer, it is essential to tailor therapy based on individual patient characteristics, comorbidities, and potential contraindications to immunotherapy, Lee concludes.