Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer
14
Issued Date
2026-04-02
Resource Type
eISSN
15334406
Scopus ID
2-s2.0-105035017291
Pubmed ID
41707170
Journal Title
New England Journal of Medicine
Volume
394
Issue
13
Start Page
1257
End Page
1269
Rights Holder(s)
SCOPUS
Bibliographic Citation
New England Journal of Medicine Vol.394 No.13 (2026) , 1257-1269
Suggested Citation
Vulsteke C., Adra N., Danchaivijitr P., Sabadash M., Rodriguez-Vida A., Zhang Z., Atduev V., Göger Y.E., Rausch S., Kang S.H., Loriot Y., Bedke J., Galsky M.D., O'Donnell P.H., von Amsberg G., Alimohamed N., Sulimka G., Gupta S., Paramonov V., Nakane K., Mihm M., Meng C., Huang C.D., Ramamurthy C., Homet Moreno B., Ullén A. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. New England Journal of Medicine Vol.394 No.13 (2026) , 1257-1269. 1269. doi:10.1056/NEJMoa2511674 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116160
Title
Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer
Author(s)
Vulsteke C.
Adra N.
Danchaivijitr P.
Sabadash M.
Rodriguez-Vida A.
Zhang Z.
Atduev V.
Göger Y.E.
Rausch S.
Kang S.H.
Loriot Y.
Bedke J.
Galsky M.D.
O'Donnell P.H.
von Amsberg G.
Alimohamed N.
Sulimka G.
Gupta S.
Paramonov V.
Nakane K.
Mihm M.
Meng C.
Huang C.D.
Ramamurthy C.
Homet Moreno B.
Ullén A.
Adra N.
Danchaivijitr P.
Sabadash M.
Rodriguez-Vida A.
Zhang Z.
Atduev V.
Göger Y.E.
Rausch S.
Kang S.H.
Loriot Y.
Bedke J.
Galsky M.D.
O'Donnell P.H.
von Amsberg G.
Alimohamed N.
Sulimka G.
Gupta S.
Paramonov V.
Nakane K.
Mihm M.
Meng C.
Huang C.D.
Ramamurthy C.
Homet Moreno B.
Ullén A.
Author's Affiliation
The University of Chicago
Karolinska Institutet
Icahn School of Medicine at Mount Sinai
Karolinska Universitetssjukhuset
Universiteit Antwerpen
Universitätsklinikum Hamburg-Eppendorf
Pfizer Inc.
Merck & Co., Inc.
Universitätsklinikum und Medizinische Fakultät Tübingen
Institut de Cancerologie Gustave Roussy
Siriraj Hospital
Necmettin Erbakan Üniversitesi
Korea University Anam Hospital
Taussig Cancer Center
Graduate School of Medicine
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Klinikum Stuttgart
Astellas Pharma US, Inc.
AZ Maria Middelares
Lviv State Oncological Regional Treatment and Diagnostic Center
Arthur J.E. Child Comprehensive Cancer Centre
Hospital del Mar
Federal Medical and Biological Agency
Hematology
Karolinska Institutet
Icahn School of Medicine at Mount Sinai
Karolinska Universitetssjukhuset
Universiteit Antwerpen
Universitätsklinikum Hamburg-Eppendorf
Pfizer Inc.
Merck & Co., Inc.
Universitätsklinikum und Medizinische Fakultät Tübingen
Institut de Cancerologie Gustave Roussy
Siriraj Hospital
Necmettin Erbakan Üniversitesi
Korea University Anam Hospital
Taussig Cancer Center
Graduate School of Medicine
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Klinikum Stuttgart
Astellas Pharma US, Inc.
AZ Maria Middelares
Lviv State Oncological Regional Treatment and Diagnostic Center
Arthur J.E. Child Comprehensive Cancer Centre
Hospital del Mar
Federal Medical and Biological Agency
Hematology
Corresponding Author(s)
Other Contributor(s)
Abstract
BACKGROUND: Patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy proceed directly to radical cystectomy with pelvic lymph-node dissection. Perioperative therapy may improve outcomes in this population. METHODS: In this phase 3, open-label trial, participants with muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based chemotherapy were randomly assigned to perioperative (neoadjuvant and adjuvant) enfortumab vedotin, an antibody-drug conjugate directed at nectin-4, plus pembrolizumab and surgery (9 total cycles of enfortumab vedotin [1.25 mg per kilogram of body weight on days 1 and 8] plus 17 total cycles of pembrolizumab [200 mg on day 1 every 3 weeks], with surgery after 3 cycles) or surgery alone (control). The primary end point was event-free survival. Key secondary end points were overall survival and pathological complete response (absence of viable tumor after surgical resection). Other secondary end points included safety. RESULTS: A total of 344 participants underwent randomization (170 in the enfortumab vedotin-pembrolizumab group and 174 in the control group). At data cutoff, median follow-up was 25.6 months (range, 11.8 to 53.7). Surgery was performed in 87.6% of participants in the enfortumab vedotin-pembrolizumab group and in 89.7% in the control group. At 2 years, estimated event-free survival was 74.7% in the enfortumab vedotin-pembrolizumab group and 39.4% in the control group (hazard ratio for an event or death, 0.40; 95% confidence interval [CI], 0.28 to 0.57; two-sided P<0.001); estimated overall survival was 79.7% and 63.1% (hazard ratio for death, 0.50; 95% CI, 0.33 to 0.74; two-sided P<0.001). A pathological complete response had occurred in 57.1% and 8.6% of the participants (estimated difference, 48.3 percentage points; 95% CI, 39.5 to 56.5; two-sided P<0.001). Adverse events occurred in all participants in the enfortumab vedotin-pembrolizumab group (grade ≥3, 71.3%; grade ≥3 drug-related, 45.5%) and in 64.8% in the control group (grade ≥3, 45.9%). CONCLUSIONS: Perioperative enfortumab vedotin plus pembrolizumab and surgery led to significantly better event-free and overall survival outcomes and a greater percentage of participants with pathological complete response than surgery alone in a predominantly cisplatin-ineligible population with muscle-invasive bladder cancer. Safety was also assessed. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-905 ClinicalTrials.gov number, NCT03924895.).