Dr Friedlander on AEs Associated With Enfortumab Vedotin in Bladder Cancer

Terence W. Friedlander, MD, genitourinary oncologist, associate clinical professor, Division of Hematology/Oncology, Robert and Virginia O’Reilly Family Endowed Professor of Medicine, University of California San Francisco (UCSF), UCSF Health; chief, Hematology-Oncology, Zuckerberg San Francisco General; associate director, Cancer Research, Helen Diller Family Comprehensive Cancer Center, discusses adverse effects (AEs) that are associated with standard agents, such as enfortumab vedotin-ejfv (Padcev), in bladder cancer.

Enfortumab vedotin combined with pembrolizumab (Keytruda) is now the recommended frontline regimen for patients with urothelial carcinoma, regardless of their cisplatin eligibility, Friedlander begins. This combination has been endorsed by the National Comprehensive Cancer Network and has shown considerable efficacy, he explains. However, there are notable AEs that clinicians should be mindful of when administering this treatment.

Although AEs associated with immunotherapy, such as those related to pembrolizumab, are generally well-known—around half of patients tolerate it well, with approximately 10% experiencing severe reactions—it is critical to recognize specific toxicity concerns with enfortumab vedotin, Friedlander states.

One of the primary toxicities observed with enfortumab vedotin is peripheral neuropathy, which affects approximately half of patients, he continues. This condition tends to emerge after 2 or 3 treatment cycles and can progressively worsen. In response, clinicians often adjust the dose, delay treatment, or even discontinue the drug if necessary, Friedlander notes. Another key risk is motor neuropathy, which affects fewer than 10% of patients but can severely impair motor functions such as handwriting and walking, he adds.

Additionally, enfortumab vedotin has been associated with skin toxicity. This includes Stevens-Johnson syndrome and toxic epidermal necrolysis, which may require hospitalization and steroid treatment, Friedlander expands. Fatalities due to these reactions have been reported. Hyperglycemia is another serious toxicity, especially for patients with preexisting diabetes. Friedlandr notes that early data from clinical trials of enfortumab vedotin revealed deaths linked to hyperglycemia and ketoacidosis in patients with poorly controlled diabetes. As a result, careful monitoring of blood glucose levels and collaboration with a patient’s primary care physician or endocrinologist is essential when using enfortumab vedotin in this population, Friedlander concludes.