Clinical Features and Risk Factors of Enfortumab Vedotin-Induced Peripheral Neuropathy in Patients With Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study (YUSHIMA Study).

OBJECTIVE

Enfortumab vedotin (EV) has emerged as a key agent in the evolving treatment paradigm for metastatic urothelial carcinoma (UC). Although EV-induced peripheral neuropathy (PN) occurs frequently, its risk factors and detailed clinical course remain unclear.

METHODS

This multicenter study included 115 consecutive patients with metastatic UC who were treated with EV monotherapy between 2021 and 2023. The incidence, risk factors, and clinical course of PN were analyzed retrospectively.

RESULTS

The median age was 74 years, and 85 (74%) were male. EV was initiated at a reduced dose of < 1.25 mg/kg in 35 (30%) patients. PN occurred in 29 (25%) patients, with a cumulative incidence of 28% at 1 year following EV induction. The maximum PN grades were 1, 2, and 3 in 9 (7.8%), 17 (15%), and 3 (2.6%) patients, respectively. The median time to PN onset was 2.7 months. In multivariable analysis, higher serum albumin levels and starting EV at full-dose were significantly associated with PN development. Of the patients who experienced Grade 1 PN and whose doses were maintained, 66.6% progressed to Grade 2 or higher. Of the patients who experienced Grade 2 PN and whose doses were maintained, 82% remained at Grade 2, while 18% ultimately progressed to Grade 3.

CONCLUSION

Higher serum albumin levels were significantly associated with EV-induced PN. Appropriate dose reduction may help prevent progression from Grade 2 to Grade 3 PN. Nevertheless, further prospective studies are warranted to determine the optimal dose management strategy for long-term EV therapy.