Cost-Effectiveness of Perioperative Enfortumab Vedotin and Pembrolizumab for Bladder Cancer.
11 affiliations
- 1The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
- 2Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee.
- 3Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland.
- 4Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
- 5Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
- 6Department of Urology, Ohio State University College of Medicine, Columbus.
- 7Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles.
- 8Department of Urology, University of North Carolina School of Medicine, Chapel Hill.
- 9Division of Urology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
- 10Department of Urology, Mayo Clinic, Rochester, Minnesota.
- 11Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut.
Abstract
Importance
Although cisplatin-based neoadjuvant chemotherapy for patients with localized muscle-invasive blader cancer (MIBC) is associated with improved survival, nearly half of these patients are ineligible for cisplatin-based chemotherapy and historically proceed to radical cystectomy (RC) without neoadjuvant chemotherapy. Perioperative enfortumab vedotin (EV) plus pembrolizumab with RC is an alternative option, but little is known about its cost-effectiveness compared with surgery alone.Objective
To evaluate the cost-effectiveness of perioperative EV plus pembrolizumab for cisplatin-ineligible patients with localized MIBC.Design, setting, and participants
This economic evaluation developed a decision-analytic Markov model that compared neoadjuvant EV plus pembrolizumab followed by RC and adjuvant EV plus pembrolizumab (intervention arm) vs RC alone (control arm). The sample consisted of simulated patients with MIBC who were ineligible for or declined cisplatin-based neoadjuvant chemotherapy. The model was informed by efficacy and safety data from the KEYNOTE-905/EV-303 trial, which had a median (range) follow-up of 25.6 (11.8-53.7) months. Analyses were performed between October 2025 and August 2026.Intervention
The 2 treatment strategies were (1) neoadjuvant EV plus pembrolizumab followed by RC and adjuvant EV plus pembrolizumab and (2) RC alone.Main outcomes and measures
Outcomes included life-years, quality-adjusted life-years (QALYs), and direct medical costs estimated from a Medicare payer perspective over a 10-year horizon. Incremental cost-effectiveness ratio (ICER) was assessed against a willingness-to-pay threshold of $100 000 per QALY. Scenario, 1-way, and probabilistic sensitivity analyses were conducted.Results
The model consisted of 10 000 patients (age at baseline, 73 years; 77 900 males [77.9%]). Over 10 years, adding perioperative EV plus pembrolizumab to treatment was associated with increased projected survival from 4.12 to 5.63 life-years per patient, quality-adjusted survival from 3.20 to 4.51 QALYs per patient, and total costs from $317 513 to $412 160. Higher upfront perioperative therapy costs were partially offset by lower postprogression treatment costs ($12 578 per patient for the intervention arm vs $238 729 per patient for the control arm). Perioperative EV plus pembrolizumab with RC achieved an ICER of $72 460 per QALY vs RC alone and therefore represented a cost-effective treatment approach. In 1-way and scenario sensitivity analyses, the cost-effectiveness result was sensitive to alternative assumptions for key factors, including time horizon length, adjuvant therapy utilization rates, patient age, postprogression treatment mix, drug costs, and health utility before disease progression. In the probabilistic sensitivity analysis, perioperative EV plus pembrolizumab with RC had a 53% probability of being cost-effective vs RC alone at the prespecified willingness-to-pay threshold of $100 000 per QALY.Conclusions and relevance
In this economic evaluation of a simulated cohort of patients with cisplatin-ineligible MIBC, clinical trial-informed modeling suggested that adopting the perioperative EV plus pembrolizumab intervention extends overall survival and quality-adjusted survival and is likely cost-effective in the US.
Related
- Skin toxicity and effectiveness of first-line enfortumab vedotin plus pembrolizumab for urothelial carcinoma: a prospective multicenter real-world study in Japan.
- Management of extravasations of enfortumab vedotin and pembrolizumab: a case report and mini review of the current literature
- Concurrent erythema multiforme and psoriasiform eruption during enfortumab vedotin plus pembrolizumab therapy for advanced urothelial carcinoma
- Confirmed Myocarditis-Myositis Overlap Without Myasthenia Gravis: Evaluating for Triple M Syndrome Following Combined Enfortumab Vedotin and Pembrolizumab Therapy.
- Circulating Tumor DNA Clearance Is Associated with Response and Survival in Metastatic Urothelial Carcinoma Treated with First-Line Enfortumab Vedotin Plus Pembrolizumab
BibTeX
@article{su2026costeffectiveness,
title = {{Cost-Effectiveness of Perioperative Enfortumab Vedotin and Pembrolizumab for Bladder Cancer.}},
author = {Zhuo Tony Su and Tyler S Garman and Carlos A Rivera Lopez and Ruchika Talwar and Raju Chelluri and Burles A Johnson and Hiten D Patel and Akshay Sood and Armine K Smith and Nirmish Singla and Jean H Hoffman-Censits and Sunil H Patel and Siamak Daneshmand and Matthew E Nielsen and Trinity J Bivalacqua and Stephen A Boorjian and Noah M Hahn and Jeffrey P Townsend and Max R Kates},
journal = {JAMA network open},
year = {2026},
month = oct,
doi = {10.1001/jamanetworkopen.2026.40370},
url = {https://europepmc.org/article/MED/42900471},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Cost-Effectiveness of Perioperative Enfortumab Vedotin and Pembrolizumab for Bladder Cancer.
AU - Zhuo Tony Su
AU - Tyler S Garman
AU - Carlos A Rivera Lopez
AU - Ruchika Talwar
AU - Raju Chelluri
AU - Burles A Johnson
AU - Hiten D Patel
AU - Akshay Sood
AU - Armine K Smith
AU - Nirmish Singla
AU - Jean H Hoffman-Censits
AU - Sunil H Patel
AU - Siamak Daneshmand
AU - Matthew E Nielsen
AU - Trinity J Bivalacqua
AU - Stephen A Boorjian
AU - Noah M Hahn
AU - Jeffrey P Townsend
AU - Max R Kates
PY - 2026
DA - 2026/10/01
JO - JAMA network open
DO - 10.1001/jamanetworkopen.2026.40370
UR - https://europepmc.org/article/MED/42900471
AB - Importance Although cisplatin-based neoadjuvant chemotherapy for patients with localized muscle-invasive blader cancer (MIBC) is associated with improved survival, nearly half of these patients are ineligible for cisplatin-based chemotherapy and historically proceed to radical cystectomy (RC) without neoadjuvant chemotherapy. Perioperative enfortumab vedotin (EV) plus pembrolizumab with RC is an alternative option, but little is known about its cost-effectiveness compared with surgery alone.Objective To evaluate the cost-effectiveness of perioperative EV plus pembrolizumab for cisplatin-ineligible patients with localized MIBC.Design, setting, and participants This economic evaluation developed a decision-analytic Markov model that compared neoadjuvant EV plus pembrolizumab followed by RC and adjuvant EV plus pembrolizumab (intervention arm) vs RC alone (control arm). The sample consisted of simulated patients with MIBC who were ineligible for or declined cisplatin-based neoadjuvant chemotherapy. The model was informed by efficacy and safety data from the KEYNOTE-905/EV-303 trial, which had a median (range) follow-up of 25.6 (11.8-53.7) months. Analyses were performed between October 2025 and August 2026.Intervention The 2 treatment strategies were (1) neoadjuvant EV plus pembrolizumab followed by RC and adjuvant EV plus pembrolizumab and (2) RC alone.Main outcomes and measures Outcomes included life-years, quality-adjusted life-years (QALYs), and direct medical costs estimated from a Medicare payer perspective over a 10-year horizon. Incremental cost-effectiveness ratio (ICER) was assessed against a willingness-to-pay threshold of $100 000 per QALY. Scenario, 1-way, and probabilistic sensitivity analyses were conducted.Results The model consisted of 10 000 patients (age at baseline, 73 years; 77 900 males [77.9%]). Over 10 years, adding perioperative EV plus pembrolizumab to treatment was associated with increased projected survival from 4.12 to 5.63 life-years per patient, quality-adjusted survival from 3.20 to 4.51 QALYs per patient, and total costs from $317 513 to $412 160. Higher upfront perioperative therapy costs were partially offset by lower postprogression treatment costs ($12 578 per patient for the intervention arm vs $238 729 per patient for the control arm). Perioperative EV plus pembrolizumab with RC achieved an ICER of $72 460 per QALY vs RC alone and therefore represented a cost-effective treatment approach. In 1-way and scenario sensitivity analyses, the cost-effectiveness result was sensitive to alternative assumptions for key factors, including time horizon length, adjuvant therapy utilization rates, patient age, postprogression treatment mix, drug costs, and health utility before disease progression. In the probabilistic sensitivity analysis, perioperative EV plus pembrolizumab with RC had a 53% probability of being cost-effective vs RC alone at the prespecified willingness-to-pay threshold of $100 000 per QALY.Conclusions and relevance In this economic evaluation of a simulated cohort of patients with cisplatin-ineligible MIBC, clinical trial-informed modeling suggested that adopting the perioperative EV plus pembrolizumab intervention extends overall survival and quality-adjusted survival and is likely cost-effective in the US.
SN - 2574-3805
ER -