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Cutaneous Toxicity and Response to Enfortumab Vedotin in Urothelial Cancer Patients - Expert Commentary

Enfortumab Vedotin (EV) is approved for patients with advanced urothelial cancer following progression after chemotherapy and PD-1 or PD-L1 inhibitor treatment. EV is an anti-nectin-4 antibody conjugated to a chemotherapeutic compound (MMAE). Various toxicities are associated with its use, including blood glucose elevation, neuropathy, and cutaneous toxicity. Commonly observed low-grade cutaneous adverse events, such as rash and pruritus, can be managed with supportive care. In this study, Vlachou et al. evaluated whether cutaneous toxicity was correlated with radiographic response in EV-treated patients.

The researchers retrospectively collected data from 56 patients who received single-agent EV. Among these, 26.8% were female, and 73.2% were male. In parallel, 51 patients also had radiographic follow-up data and were therefore included in the efficacy analysis. The mean age among patients was 70.1 years, and 84% were at or past their third-line treatment. With respect to toxicity, 48% of patients experienced any-grade cutaneous toxicity during early cycles. Sixteen patients developed grade 1 skin toxicity, seven developed grade 2, two developed grade 3, two developed grade 4, and three developed severe toxicities that required hospitalization. The incidence of cutaneous toxicity was similar between bladder cancer patients (44.1%) and upper tract urothelial carcinoma patients (50%). Those who developed cutaneous toxicity had a significantly higher baseline weight and body mass index.

The efficacy analysis of radiographic follow-up data showed a response rate of 41.2%, and the disease control rate was 68.7%. The response rate was 57.7% for patients with cutaneous toxicity and 24% for those without. All three patients who exhibited complete response developed a rash, while three patients who developed skin toxicity subsequently had a partial response. The two patients who did not experience skin toxicity were frail and received a reduced dose, with one patient experiencing stable disease and the other experiencing disease progression. Median progression-free survival was 6 months for all patients with cutaneous toxicity and 4.5 months for those without (non-significant difference).

Overall, these findings point towards a link between cutaneous toxicity and response to EV. However, the sample size and the study's retrospective single-center design limit the generalizability of the study findings. Validation studies on much larger patient cohorts will be needed to confirm this association. Studies into potential mechanisms underlying this link will uncover the biological determinants of treatment response.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

Reference:

  1. Vlachou E, Matoso A, McConkey D, et al. Enfortumab Vedotin–related Cutaneous Toxicity and Radiographic Response in Patients with Urothelial Cancer: A Single-center Experience and Review of the Literature. European urology open science (Online). 2023;49:100-103.
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