Dr Siefker-Radtke on the Safety of Enfortumab Vedotin Plus Pembrolizumab in Bladder Cancer

Arlene O. Siefker-Radtke, MD, professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses toxicities associated with the combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) in patients with metastatic bladder cancer.

Enfortumab vedotin combined with pembrolizumab carries a boxed warning due to the risk of Stevens-Johnson Syndrome, which is a severe skin reaction, Siefker-Radtke begins. This reaction may be linked to enfortumab vedotin’s targeting of Nectin-4, which is expressed in skin tissue, leading to skin desquamation in affected patients, according to Siefker-Radtke. Additionally, there is increased toxicity associated with enfortumab vedotin in patients with borderline liver function, she explains, adding that it is recommended to avoid using enfortumab vedotin in patients with moderate-to-severe liver dysfunction. Other antibody-drug conjugates using the vedotin payload have been associated with increased liver toxicity, indicating potential risks in this patient population, Siefker-Radtke states.

For patients with a borderline Child-Pugh score of A to B, initiating treatment with a reduced dose of enfortumab vedotin may be attempted; however, many patients experience significant toxicity, making treatment continuation challenging, she notes. Monitoring for skin toxicity is crucial during treatment; if patients exhibit blistering, peeling of the skin, or a diffuse beefy erythematous rash, this may signal the onset of severe skin toxicity and warrant dose adjustment or discontinuation, Siefker-Radtke reports. Hyperglycemia should also be closely monitored, as elevated fasting glucose levels above 250 mg/dL may indicate toxicity and increase the risk of insulin-resistant diabetic ketoacidosis, Siefker-Radtke emphasizes.

Furthermore, patients with underlying liver cirrhosis require careful monitoring and consideration when administering enfortumab vedotin, especially those with a truly cirrhotic liver, Siefker-Radtke expands. Given the challenges posed by toxicity in patients with borderline Child-Pugh scores of A to B, alternative treatment options, such as gemcitabine/cisplatin plus nivolumab (Opdivo) should be considered to optimize safety and efficacy, she says. These recommendations underscore the importance of vigilant monitoring and personalized treatment strategies to mitigate risks associated with enfortumab vedotin and pembrolizumab combination therapy, particularly in vulnerable patient populations, Siefker-Radtke concludes.