Dr Lee on Safety Considerations for Enfortumab Vedotin in Metastatic Urothelial Cancer

John K. Lee, MD, PhD, assistant professor, medicine, University of California, San Francisco (UCSF); director, Bladder Cancer Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses safety considerations for enfortumab vedotin-ejfv (Padcev), an antibody-drug conjugate (ADC) in the treatment of metastatic urothelial cancer.

Enfortumab vedotin targets NECTIN-4, a protein expressed in tumor cells that is also expressed in normal tissues, including the gastrointestinal (GI) tract, esophagus, and skin, which contributes to its unique adverse effect (AE) profile.

Lee explains that one of the most concerning AEs associated with enfortumab vedotin is the risk of severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These toxicities require prompt identification and management, as they can be life-threatening if not addressed early, he says, noting that dermatologic monitoring is crucial throughout the treatment course to mitigate potential severe skin toxicities.

NECTIN-4 expression in the GI tract can also lead to AEs such as diarrhea, nausea, and mucositis, Lee continues. These symptoms can significantly impact a patient's quality of life and may require supportive care measures, including antiemetics and hydration.

Peripheral neuropathy is a common and progressive toxicity associated with enfortumab vedotin, often related to its chemotherapeutic component. The development of neuropathy can be debilitating and affect patients' daily activities and overall quality of life, Lee explains. Vigilance in monitoring for early signs of neuropathy is essential, and dose modifications or discontinuation may be required based on the severity of symptoms.

Since enfortumab vedotin is approved in the frontline setting in combination with pembrolizumab (Keytruda), the use of the antibody-drug conjugate with an immune checkpoint inhibitor adds another layer of safety considerations. Immune-related AEs (irAEs), which can range from mild to severe, are also something to monitor with this combination, Lee says. These irAEs also necessitate close monitoring and a proactive management approach, including the use of corticosteroids or other immunosuppressive agents when appropriate.

Lee concludes that the safety profile of enfortumab vedotin necessitates careful monitoring for these specific AEs to optimize patient outcomes and minimize treatment-related toxicities.