222P - The association between response to enfortumab vedotin and peripheral neuropathy: A multicenter retrospective study in Japan

Background

Enfortumab vedotin (EV) was approved for patients with unresectable and/or metastatic urothelial carcinoma (u/mUC) who progressed after anti-cancer therapy on September 2021 in Japan. So far, the association between occurrence of EV-related side effect and clinical outcome has not been well-understood.

Methods

We identified 97 u/mUC patients treated with EV therapy at our 5 institutions from the approval to December 2022. Median age was 71 years (range: 29-85 years). The median follow-up periods were 7.0 (range: 1.4-16.0) months. We evaluated the association between treatment response to EV and the side-effect profile in our u/mUC patients treated with EV.

Results

Overall, best clinical response to EV therapy was 43.3% (42/97 patients). Among patients’ baseline background, type of previous immune-checkpoint inhibitor was only associated with best clinical response to EV. Any grade of treatment-related peripheral neuropathy, skin disorder, dysgeusia, gastrointestinal disorder, hyperglycemia, fatigue, and alopecia occurred in 34 patients (35.1%), 16 (62.9%), 36 (37.1%), 29 (29.9%), 10 (10.3%), 15 (15.5%), 16 (16.5%), respectively. Among these side effects of EV, the occurrence of peripheral neuropathy and alopecia were significantly associated with best clinical response to EV (p=0.032, and p=0.030, respectively). Furthermore, patients who had peripheral neuropathy after EV treatment had significantly longer progression-free survival (PFS) and overall survival (OS) as compared to those without (p=0.017, and p=0.008, respectively). In multivariate Cox regression analysis, the occurrence of peripheral neuropathy after EV treatment in addition to presence of peritoneal dissemination before EV treatment was independently associated with PFS (hazard ratio=0.458, p=0.008) and OS (hazard ratio=0.296, p=0.005).

Conclusions

The occurrence of treatment related peripheral neuropathy might predict the efficacy of EV therapy in u/mUC patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N. Hayakawa: Financial Interests, Personal, Invited Speaker: Astellas, Takeda, Merck; Financial Interests, Institutional, Other, Postmarketing Product Surveillance: MSD; Financial Interests, Institutional, Research Grant: Takeda, Nippon Kayaku, Kyorin, Taiho. G. Kaneko: Financial Interests, Personal, Invited Speaker: Astellas. W. Obara: Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Pfizer, Ono, Taiho. Y. Kondo: Financial Interests, Personal, Invited Speaker: Astellas, Merck Biopharma, Nippon Kayaku. E. Kikuchi: Financial Interests, Personal, Invited Speaker: MSD, Bristol, Janssen, Astellas, Merck Biopharm, Nippon Kayaku, Pfizer; Financial Interests, Personal, Advisory Board: Astellas, MSD, Bristol; Financial Interests, Institutional, Research Grant: TAKEDA, Nippon Kayaku, Kyorin, Taiho, NIPPON SHINYAKU. All other authors have declared no conflicts of interest.