Incidence, risk factors, and clinical implications of enfortumab vedotin-related cutaneous toxicity in urothelial carcinoma: a large-scale, real-world study in Japan
Background: Enfortumab vedotin (EV), an innovative antibody–drug conjugate targeting Nectin-4, has emerged as a breakthrough therapy for locally advanced or metastatic urothelial carcinoma (la/mUC). However, EV-related cutaneous toxicity (EVRCT) remains a significant concern because of Nectin-4 expr...
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2025-03-01
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| author | Y. Kita T. Hara T. Kawahara K. Hashimoto Y. Matsushita H. Ito T. Abe A. Igarashi S. Shimura T. Sazuka A. Yokomizo N. Takaoka M. Kato T. Hazama M. Miyake Y. Sugino J. Mutaguchi A. Takahashi Y. Shiraishi S. Tatarano Y. Takai T. Mochizuki S. Nakanishi K. Mori T. Yoshida T. Hayashi H. Otsuka T. Anami K. Okasho K. Daizumoto M. Kobayashi I. Kobayashi J. Watanabe N. Nishiyama T. Shibuya Y. Matsui H. Nishiyama H. Kitamura T. Kobayashi |
| author_facet | Y. Kita T. Hara T. Kawahara K. Hashimoto Y. Matsushita H. Ito T. Abe A. Igarashi S. Shimura T. Sazuka A. Yokomizo N. Takaoka M. Kato T. Hazama M. Miyake Y. Sugino J. Mutaguchi A. Takahashi Y. Shiraishi S. Tatarano Y. Takai T. Mochizuki S. Nakanishi K. Mori T. Yoshida T. Hayashi H. Otsuka T. Anami K. Okasho K. Daizumoto M. Kobayashi I. Kobayashi J. Watanabe N. Nishiyama T. Shibuya Y. Matsui H. Nishiyama H. Kitamura T. Kobayashi |
| author_sort | Y. Kita |
| collection | DOAJ |
| description | Background: Enfortumab vedotin (EV), an innovative antibody–drug conjugate targeting Nectin-4, has emerged as a breakthrough therapy for locally advanced or metastatic urothelial carcinoma (la/mUC). However, EV-related cutaneous toxicity (EVRCT) remains a significant concern because of Nectin-4 expression in skin tissue. This study aimed to understand the incidence, risk factors, and clinical implications of EVRCT, focusing on relationships with treatment efficacy, using one of the largest real-world datasets from a Japanese la/mUC patient cohort. Materials and methods: Data from 207 la/mUC patients treated with EV, mainly as a third-line therapy between 2020 and 2023, were analyzed. Multivariate logistic regression and propensity score matching (PSM) were used to assess the risk factors and impact of EVRCTs on patient overall survival (OS) and progression-free survival (PFS). Results: EVRCTs were observed in 59.9% of patients, with 83% occurring within the first 3 months, defined as early-phase EVRCTs (epEVRCTs). Multivariate analysis identified better Eastern Cooperative Oncology Group performance status (ECOG PS = 0), higher hemoglobin levels (≥11 g/dl), and the standard initial dose (1.25 mg/kg) as significant risk factors for epEVRCTs. Patients with epEVRCTs demonstrated significantly improved PFS and OS compared with those without. Post-PSM analysis confirmed longer OS for patients with epEVRCTs, particularly those with mild (grade 1) toxicities, suggesting that these reactions may be significantly linked to favorable treatment outcomes. Conclusions: Our data suggest that epEVRCTs are common and correlate with better clinical outcomes in la/mUC patients treated with EV, underscoring the importance of proactive EVRCT management to optimize therapeutic benefits. |
| format | Article |
| id | doaj-art-b38155bb1fd64cf38bc3e9086e27c782 |
| institution | OA Journals |
| issn | 2949-8201 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | ESMO Real World Data and Digital Oncology |
| spelling | doaj-art-b38155bb1fd64cf38bc3e9086e27c7822025-08-20T02:19:23ZengElsevierESMO Real World Data and Digital Oncology2949-82012025-03-01710009410.1016/j.esmorw.2024.100094Incidence, risk factors, and clinical implications of enfortumab vedotin-related cutaneous toxicity in urothelial carcinoma: a large-scale, real-world study in JapanY. Kita0T. Hara1T. Kawahara2K. Hashimoto3Y. Matsushita4H. Ito5T. Abe6A. Igarashi7S. Shimura8T. Sazuka9A. Yokomizo10N. Takaoka11M. Kato12T. Hazama13M. Miyake14Y. Sugino15J. Mutaguchi16A. Takahashi17Y. Shiraishi18S. Tatarano19Y. Takai20T. Mochizuki21S. Nakanishi22K. Mori23T. Yoshida24T. Hayashi25H. Otsuka26T. Anami27K. Okasho28K. Daizumoto29M. Kobayashi30I. Kobayashi31J. Watanabe32N. Nishiyama33T. Shibuya34Y. Matsui35H. Nishiyama36H. Kitamura37T. Kobayashi38Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Urology, Kobe University, Kobe, JapanDepartment of Urology, University of Tsukuba, Tsukuba, JapanDepartment of Urology, Sapporo Medical University, Sapporo, JapanDepartment of Urology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Urology, Yokohama City University, Yokohama, JapanDepartment of Urology, Hokkaido University, Sapporo, JapanDepartment of Urology, Kobe City Medical Center General Hospital, Kobe, JapanDepartment of Urology, Kitasato University, Kanagawa, JapanDepartment of Urology, Chiba University, Chiba, JapanDepartment of Urology, Harasanshin Hospital, Fukuoka, JapanDepartment of Urology, Tenri Hospital, Tenri, JapanDepartment of Urology, Osaka Metropolitan University, Osaka, JapanDepartment of Urology, Japanese Red Cross Wakayama Medical Center, Wakayama, JapanDepartment of Urology, Nara Medical University, Nara, JapanDepartment of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, JapanDepartment of Urology, Kyushu University, Fukuoka, JapanDepartment of Urology, Hakodate Goryoukaku Hospital, Hakodate, JapanDepartment of Urology, Shizuoka General Hospital, Shizuoka, JapanDepartment of Urology, Kagoshima University, Kagoshima, JapanDepartment of Urology, Yamagata University, Tsuruoka, JapanDepartment of Urology, University of Yamanashi, Chuo, JapanDepartment of Urology, University of the Ryukyus, Nakagami, JapanDepartment of Urology, Jikei University School of Medicine, Tokyo, JapanDepartment of Urology, Shiga General Hospital, Moriyama, JapanDepartment of Urology, Hiroshima University, Hiroshima, JapanDepartment of Urology, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, JapanDepartment of Urology, Kumamoto University, Kumamoto, JapanDepartment of Urology, Hirakata Kohsai Hospital, Hirakata, JapanDepartment of Urology, Tokushima University, Tokushima, JapanDepartment of Urology, Akita University, Akita, JapanDepartment of Urology, Aichi Medical University, Nagakute, JapanDepartment of Urology, Toyooka Hospital, Toyooka, JapanDepartment of Urology, University of Toyama, Toyama, JapanDepartment of Urology, Oita University, Yufu, JapanDepartment of Urology, National Cancer Center Hospital, Tokyo, JapanDepartment of Urology, University of Tsukuba, Tsukuba, JapanDepartment of Urology, University of Toyama, Toyama, JapanDepartment of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Correspondence to: Dr Takashi Kobayashi, Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Tel: +81-075-751-3337; Fax: +81-075-751-3740Background: Enfortumab vedotin (EV), an innovative antibody–drug conjugate targeting Nectin-4, has emerged as a breakthrough therapy for locally advanced or metastatic urothelial carcinoma (la/mUC). However, EV-related cutaneous toxicity (EVRCT) remains a significant concern because of Nectin-4 expression in skin tissue. This study aimed to understand the incidence, risk factors, and clinical implications of EVRCT, focusing on relationships with treatment efficacy, using one of the largest real-world datasets from a Japanese la/mUC patient cohort. Materials and methods: Data from 207 la/mUC patients treated with EV, mainly as a third-line therapy between 2020 and 2023, were analyzed. Multivariate logistic regression and propensity score matching (PSM) were used to assess the risk factors and impact of EVRCTs on patient overall survival (OS) and progression-free survival (PFS). Results: EVRCTs were observed in 59.9% of patients, with 83% occurring within the first 3 months, defined as early-phase EVRCTs (epEVRCTs). Multivariate analysis identified better Eastern Cooperative Oncology Group performance status (ECOG PS = 0), higher hemoglobin levels (≥11 g/dl), and the standard initial dose (1.25 mg/kg) as significant risk factors for epEVRCTs. Patients with epEVRCTs demonstrated significantly improved PFS and OS compared with those without. Post-PSM analysis confirmed longer OS for patients with epEVRCTs, particularly those with mild (grade 1) toxicities, suggesting that these reactions may be significantly linked to favorable treatment outcomes. Conclusions: Our data suggest that epEVRCTs are common and correlate with better clinical outcomes in la/mUC patients treated with EV, underscoring the importance of proactive EVRCT management to optimize therapeutic benefits.http://www.sciencedirect.com/science/article/pii/S2949820124000729EV-related cutaneous toxicityincidencerisk factorclinical outcome |
| spellingShingle | Y. Kita T. Hara T. Kawahara K. Hashimoto Y. Matsushita H. Ito T. Abe A. Igarashi S. Shimura T. Sazuka A. Yokomizo N. Takaoka M. Kato T. Hazama M. Miyake Y. Sugino J. Mutaguchi A. Takahashi Y. Shiraishi S. Tatarano Y. Takai T. Mochizuki S. Nakanishi K. Mori T. Yoshida T. Hayashi H. Otsuka T. Anami K. Okasho K. Daizumoto M. Kobayashi I. Kobayashi J. Watanabe N. Nishiyama T. Shibuya Y. Matsui H. Nishiyama H. Kitamura T. Kobayashi Incidence, risk factors, and clinical implications of enfortumab vedotin-related cutaneous toxicity in urothelial carcinoma: a large-scale, real-world study in Japan ESMO Real World Data and Digital Oncology EV-related cutaneous toxicity incidence risk factor clinical outcome |
| title | Incidence, risk factors, and clinical implications of enfortumab vedotin-related cutaneous toxicity in urothelial carcinoma: a large-scale, real-world study in Japan |
| title_full | Incidence, risk factors, and clinical implications of enfortumab vedotin-related cutaneous toxicity in urothelial carcinoma: a large-scale, real-world study in Japan |
| title_fullStr | Incidence, risk factors, and clinical implications of enfortumab vedotin-related cutaneous toxicity in urothelial carcinoma: a large-scale, real-world study in Japan |
| title_full_unstemmed | Incidence, risk factors, and clinical implications of enfortumab vedotin-related cutaneous toxicity in urothelial carcinoma: a large-scale, real-world study in Japan |
| title_short | Incidence, risk factors, and clinical implications of enfortumab vedotin-related cutaneous toxicity in urothelial carcinoma: a large-scale, real-world study in Japan |
| title_sort | incidence risk factors and clinical implications of enfortumab vedotin related cutaneous toxicity in urothelial carcinoma a large scale real world study in japan |
| topic | EV-related cutaneous toxicity incidence risk factor clinical outcome |
| url | http://www.sciencedirect.com/science/article/pii/S2949820124000729 |
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