Dermatologic events associated with the use of enfortumab vedotin for locally advanced/metastatic urothelial carcinoma (la/mUC) are common, and there is a potential for rare but possibly fatal cutaneous adverse reactions. These findings were described in a report published in The Oncologist.
In the United States, metastatic urothelial cancer historically has carried poor survival outcomes, highlighting the importance of treatments offering efficacy and tolerability. Enfortumab vedotin has demonstrated positive survival benefits in clinical trials involving la/mUC.
A target of enfortumab vedotin is Nectin-4, a molecule ordinarily expressed in skin, as well as various internal structures of the body. High expression of Nectin-4 is seen with many cancers. Enfortumab vedotin can promote apoptosis through delivery of monomethyl auristatin E to cells that express Nectin-4. However, expression of Nectin-4 in the skin can be associated with dermatologic effects from treatment with a Nectin-4-targeting agent.
Dermatologic events that may be associated with enfortumab vedotin range from dry skin and alopecia to erythematous pruritic papules and others. Use of the agent also has the potential to lead to certain severe, possibly fatal, skin reactions. “Across enfortumab vedotin clinical trials, rare events of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) occurred and are included in the boxed warning of the US prescribing information for enfortumab vedotin,” the researchers explained.
In the phase 3 EV-301 clinical trial of enfortumab vedotin (ClinicalTrials.gov Identifier: NCT03474107), treatment-related skin reactions occurred in 47% of patients, with 15% of patients experiencing grade 3 or 4 reactions. Any-grade severe cutaneous adverse reactions occurred in 20% of patients, and 5% of patients had grade 3 or 4 severe cutaneous adverse reactions. Treatment withdrawal owing to any skin reaction occurred in 4% of patients.
The investigators’ recommendations for managing dermatologic events were based on severity and type. Their recommendations included supportive care, topical or oral corticosteroids, anti-infective agents, biopsies, dermatologic consultations, and other strategies. They advised that grade 4 or recurrent grade 3 reactions, or confirmed SJS or TEN, should result in permanent discontinuation of treatment and may require specialized inpatient care.
“By having an awareness of the pathophysiology of enfortumab vedotin-related dermatologic events as well as protocols for prevention and management, oncologists should be better equipped to educate, appropriately monitor, and manage patients who develop these reactions to minimize toxicity and maximize clinical benefit,” the investigators stated. They also recommended that patients and caregivers be educated regarding the features of dermatologic events.
Disclosures: This research was supported by Seagen Inc. Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Lacouture ME, Patel AB, Rosenberg JE, O’Donnell PH. Management of dermatologic events associated with the nectin-4-directed antibody-drug conjugate enfortumab vedotin. Oncologist. 2022;27(3):e223-e232. doi:10.1093/oncolo/oyac001