Skip to content
DraconiticResearch
Search Sources API
190,332 studies31 sourcesUpdated 20 min ago
Peer-reviewedCC BY 4.0JAMA Network Open

Initial Enfortumab Vedotin Dose Reduction and Outcomes in Pretreated Advanced Urothelial Carcinoma

  • In-Ho Kim1
  • Chang Gon Kim2
  • Jungmin Jo3
  • Eun Hee Jung4
  • Joo-Hwan Park5
  • Woo Kyun Bae6
  • Seok Jae Huh7
  • Yoon Ji Choi8
  • Hyeon-Su Im9
  • Hyo Jin Lee10
  • Kyoungmin Lee11
  • Min-Young Lee12
6 more authors
  • Ji Hyun Park13
  • Hee Jun Kim14
  • Haa-Na Song15
  • Hongsik Kim16
  • Seong-Hoon Shin17
  • Inkeun Park18
18 affiliations
  1. 1Division of Medical Oncology, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
  2. 2Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
  3. 3Division of Medical Oncology, Ewha Womans University College of Medicine, Seoul, Republic of Korea
  4. 4Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
  5. 5Division of Medical Oncology, Department of Internal Medicine, Gil Medical Center, College of Medicine, Gachon University, Incheon, Republic of Korea
  6. 6Division of Hematology-Oncology, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Republic of Korea
  7. 7Division of Hematology-Oncology, Department of Internal Medicine, Dong-A University College of Medicine, Busan, Republic of Korea
  8. 8Division of Hematology-Oncology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
  9. 9Division of Hematology and Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
  10. 10Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Republic of Korea
  11. 11Division of Oncology/Hematology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
  12. 12Division of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
  13. 13Department of Hemato-oncology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea
  14. 14Division of Hematology/Medical Oncology, Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea
  15. 15Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Republic of Korea
  16. 16Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Republic of Korea
  17. 17Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Republic of Korea
  18. 18Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Open at sourceDOICite

Abstract

Importance: Initial enfortumab vedotin (EV) dose selection is increasingly relevant in advanced urothelial carcinoma (UC). Reduced starting doses may be selected for some patients, but their associations with clinical outcomes and tolerability remain uncertain.

Objective: To evaluate the association of physician-selected initial EV dose reduction with clinical outcomes among patients with advanced UC.

Design, Setting, and Participants: This retrospective multicenter cohort study of patients with advanced UC who initiated EV monotherapy after platinum-based chemotherapy and immune checkpoint inhibition was conducted at 18 institutions in Korea from January 1, 2023, to May 31, 2025, with follow-up through May 31, 2026. Data were analyzed in June 2026.

Exposures: Initial EV dose reduction at first administration, before treatment-related toxicity. The primary comparison was reduced-dose (≥10% reduction) vs full-dose (<10% reduction) EV monotherapy; post hoc analyses used less than 10%, 10% to 20%, and greater than 20% categories.

Main Outcomes and Measures: Progression-free survival (PFS) and overall survival (OS) were the primary outcomes. Secondary outcomes included objective response and treatment-emergent peripheral neuropathy (PN).

Results: Among 368 patients (median [IQR] age, 68.0 [62.0-74.0] years; 267 male [72.6%] and 101 female [27.4%]), median (IQR) follow-up was 15.4 (8.4-20.0) months. Median PFS was 5.7 months in the reduced-dose group and 6.3 months in the full-dose group (adjusted hazard ratio [HR], 1.24; 95% CI, 0.95-1.61); median OS was 10.1 and 10.5 months, respectively (adjusted HR, 1.07; 95% CI, 0.81-1.43). Objective response occurred in 65 of 146 response-evaluable patients (44.5%) in the reduced-dose group and 95 of 179 (53.1%) in the full-dose group. Grade 3 or higher PN occurred in 6 of 170 reduced-dose patients (3.5%) and 20 of 198 full-dose patients (10.1%) (adjusted odds ratio, 0.26; 95% CI, 0.09-0.73). In post hoc analyses, reductions exceeding 20% were associated with shorter PFS compared with the full-dose group (adjusted HR, 1.40; 95% CI, 1.01-1.95), although the overall 3-group comparison was not statistically significant.

Conclusions and Relevance: In this multicenter cohort study, physician-selected initial EV dose reduction was not significantly associated with survival or response outcomes. These findings do not establish equivalence or warrant routine initial dose reduction. The lower incidence of severe PN and the exploratory PFS signal with reductions exceeding 20% are hypothesis-generating and require prospective validation.

Related

  1. Sex-based differences in clinical outcomes of enfortumab vedotin and NECTIN-4 expression in urothelial cancer
    Tarek Taha, Ayelet Alpert, Jalal Baranseh +17
    Nature CommunicationsPeer-reviewedCC BY 4.0Full textSurgery & anaesthesiaCrossref
  2. Skin toxicity and effectiveness of first-line enfortumab vedotin plus pembrolizumab for urothelial carcinoma: a prospective multicenter real-world study in Japan.
    K Tamura, T Tsujino, R Taoka +24
    ESMO real world data and digital oncologyPeer-reviewedCC BYFull textSurgery & anaesthesiaEurope PMC
  3. Circulating Tumor DNA Clearance Is Associated with Response and Survival in Metastatic Urothelial Carcinoma Treated with First-Line Enfortumab Vedotin Plus Pembrolizumab
    Adam Khorasanchi, Sayan Mullick Chowdhury, Eric Fei Hong +19
    CancersPeer-reviewedCC BY 4.0OncologyCrossref
  4. Skin Toxic Effects and Survival With Enfortumab Vedotin-Pembrolizumab in Advanced Urothelial Carcinoma.
    Zachariah Thomas, Cindy Y Jiang, Patrick J Speck +25
    JAMA network openPeer-reviewedCC BY-NC-NDFull textSurgery & anaesthesiaEurope PMCCrossref
  5. A urothelial cell carcinoma in the abdominal cavity after salpingectomy for tubo-ovarian carcinoma risk reduction in a BRCA1 pathogenic variant carrier
    Tamar A. Gootzen, Alda Birgsdottir, Miranda P. Steenbeek +4
    Gynecologic oncology reportsPeer-reviewedCC BY-NC-NDFull textGeneral medicineEurope PMC

Cite

BibTeXRIS
BibTeX
@article{kim2026initial,
  title = {{Initial Enfortumab Vedotin Dose Reduction and Outcomes in Pretreated Advanced Urothelial Carcinoma}},
  author = {In-Ho Kim and Chang Gon Kim and Jungmin Jo and Eun Hee Jung and Joo-Hwan Park and Woo Kyun Bae and Seok Jae Huh and Yoon Ji Choi and Hyeon-Su Im and Hyo Jin Lee and Kyoungmin Lee and Min-Young Lee and Ji Hyun Park and Hee Jun Kim and Haa-Na Song and Hongsik Kim and Seong-Hoon Shin and Inkeun Park},
  journal = {JAMA Network Open},
  year = {2026},
  month = oct,
  doi = {10.1001/jamanetworkopen.2026.39846},
  url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855572},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Initial Enfortumab Vedotin Dose Reduction and Outcomes in Pretreated Advanced Urothelial Carcinoma
AU  - In-Ho Kim
AU  - Chang Gon Kim
AU  - Jungmin Jo
AU  - Eun Hee Jung
AU  - Joo-Hwan Park
AU  - Woo Kyun Bae
AU  - Seok Jae Huh
AU  - Yoon Ji Choi
AU  - Hyeon-Su Im
AU  - Hyo Jin Lee
AU  - Kyoungmin Lee
AU  - Min-Young Lee
AU  - Ji Hyun Park
AU  - Hee Jun Kim
AU  - Haa-Na Song
AU  - Hongsik Kim
AU  - Seong-Hoon Shin
AU  - Inkeun Park
PY  - 2026
DA  - 2026/10/21
JO  - JAMA Network Open
DO  - 10.1001/jamanetworkopen.2026.39846
UR  - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855572
AB  - Importance: Initial enfortumab vedotin (EV) dose selection is increasingly relevant in advanced urothelial carcinoma (UC). Reduced starting doses may be selected for some patients, but their associations with clinical outcomes and tolerability remain uncertain.  Objective: To evaluate the association of physician-selected initial EV dose reduction with clinical outcomes among patients with advanced UC.  Design, Setting, and Participants: This retrospective multicenter cohort study of patients with advanced UC who initiated EV monotherapy after platinum-based chemotherapy and immune checkpoint inhibition was conducted at 18 institutions in Korea from January 1, 2023, to May 31, 2025, with follow-up through May 31, 2026. Data were analyzed in June 2026.  Exposures: Initial EV dose reduction at first administration, before treatment-related toxicity. The primary comparison was reduced-dose (≥10% reduction) vs full-dose (<10% reduction) EV monotherapy; post hoc analyses used less than 10%, 10% to 20%, and greater than 20% categories.  Main Outcomes and Measures: Progression-free survival (PFS) and overall survival (OS) were the primary outcomes. Secondary outcomes included objective response and treatment-emergent peripheral neuropathy (PN).  Results: Among 368 patients (median [IQR] age, 68.0 [62.0-74.0] years; 267 male [72.6%] and 101 female [27.4%]), median (IQR) follow-up was 15.4 (8.4-20.0) months. Median PFS was 5.7 months in the reduced-dose group and 6.3 months in the full-dose group (adjusted hazard ratio [HR], 1.24; 95% CI, 0.95-1.61); median OS was 10.1 and 10.5 months, respectively (adjusted HR, 1.07; 95% CI, 0.81-1.43). Objective response occurred in 65 of 146 response-evaluable patients (44.5%) in the reduced-dose group and 95 of 179 (53.1%) in the full-dose group. Grade 3 or higher PN occurred in 6 of 170 reduced-dose patients (3.5%) and 20 of 198 full-dose patients (10.1%) (adjusted odds ratio, 0.26; 95% CI, 0.09-0.73). In post hoc analyses, reductions exceeding 20% were associated with shorter PFS compared with the full-dose group (adjusted HR, 1.40; 95% CI, 1.01-1.95), although the overall 3-group comparison was not statistically significant.  Conclusions and Relevance: In this multicenter cohort study, physician-selected initial EV dose reduction was not significantly associated with survival or response outcomes. These findings do not establish equivalence or warrant routine initial dose reduction. The lower incidence of severe PN and the exploratory PFS signal with reductions exceeding 20% are hypothesis-generating and require prospective validation.
SN  - 2574-3805
ER  -