Enfortumab Vedotin/Pembrolizumab Cost Effective in Bladder Cancer

According to findings published in JAMA Network Open, perioperative enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) with radical cystectomy had an incremental cost-effectiveness ratio (ICER) of $72,460 per quality-adjusted life-year (QALY) gained vs radical cystectomy alone in cisplatin-ineligible muscle-invasive bladder cancer (MIBC). The ICER fell below the prespecified willingness-to-pay threshold of $100,000 per QALY from a US Medicare payer perspective.¹

Nearly half of patients with MIBC are ineligible for cisplatin-based neoadjuvant chemotherapy and historically proceed to radical cystectomy without neoadjuvant therapy, the authors wrote in the publication. In the phase 3 KEYNOTE-905/EV-303 trial (NCT03924895), neoadjuvant enfortumab vedotin plus pembrolizumab followed by radical cystectomy and adjuvant therapy improved event-free survival (EFS) and overall survival (OS) compared with radical cystectomy alone.² The FDA approved the regimen for cisplatin-ineligible MIBC in November 2025 after earlier trial results.³ In July 2026, the agency expanded the indication to cisplatin-eligible patientsbased on the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124).⁴

Model Projects Gains in Survival and Quality-Adjusted Survival

The economic evaluation used a decision-analytic Markov model to compare neoadjuvant enfortumab vedotin plus pembrolizumab followed by radical cystectomy and adjuvant enfortumab vedotin plus pembrolizumab (intervention arm) with radical cystectomy alone (control arm).¹ The model included 10,000 simulated patients with a baseline age of 73 years. Efficacy and safety inputs came from KEYNOTE-905/EV-303, which had a median follow-up of 25.6 months (range, 11.8-53.7).

The model used a 3-week cycle length and 3 health states: preprogression, postprogression, and death. Outcomes were assessed over a 10-year horizon from a US Medicare payer perspective, with costs adjusted to 2025 US dollars and future life-years, QALYs, and costs discounted at 3% annually. Beyond 4 years of trial follow-up, the model assumed no sustained EFS or OS benefit for the intervention arm.

Over 10 years, the intervention was associated with an increase in projected survival from 4.12 to 5.63 life-years per patient and an increase in quality-adjusted survival from 3.20 to 4.51 QALYs per patient vs radical cystectomy alone.¹

Higher Upfront Costs Largely Offset by Lower Postprogression Spending

Neoadjuvant and adjuvant therapies cost $336,907 per patient in the intervention arm, compared with $27,974 for adjuvant therapy per patient in the control arm.¹ Postprogression treatment costs were $12,578 per patient in the intervention arm vs $238,729 per patient in the control arm.¹

Total per-patient costs were $412,160 in the intervention arm and $317,513 in the control arm, an incremental difference of $94,646. The resulting ICER of $72,460 per QALY was below the $100,000 per QALY threshold, and the investigators concluded the regimen was cost-effective compared with radical cystectomy alone from the Medicare perspective.

In the probabilistic sensitivity analysis, which used 10,000 Monte Carlo simulations, the intervention arm had a 53% probability of being cost-effective at the $100,000 per QALY threshold.

Shorter Horizon, Universal Adjuvant Use Exceed Threshold

In a prespecified 5-year scenario, life-years increased from 2.89 to 3.62 per patient and QALYs from 2.21 to 2.83 per patient. The ICER rose to $229,658 per QALY, exceeding the $100,000 per QALY threshold. In a lifetime scenario, life-years increased from 4.24 to 6.16 and QALYs from 3.30 to 4.95, with an ICER of $59,218 per QALY.¹

In a third scenario, all patients in the intervention arm who underwent radical cystectomy were assumed to start adjuvant therapy, compared with 67.1% reported in the trial. This scenario changed costs only, and EFS and OS were held unchanged. Total per-patient costs in the intervention arm rose to $510,523, of which $434,142 (85%) was attributable to neoadjuvant and adjuvant enfortumab vedotin plus pembrolizumab, and the ICER was $151,046 per QALY, above the threshold.

One-way sensitivity analyses identified the proportion of patients receiving adjuvant therapy, patient age at baseline, drug costs, postprogression treatment use, and preprogression health utility among the parameters with the greatest effect on the ICER. When the adjuvant proportion in the intervention arm was changed from 35% to 82%, the ICER ranged from $7333 per QALY to $139,474 per QALY.

Extrapolation, Adherence, and Toxicity as Key Limitations

The authors wrote that the results should be validated as longer-term outcome data become available, noting that the model extrapolated survival curves beyond the trial’s median follow-up using parametric functions. In KEYNOTE-905/EV-303, fewer than 60% of patients assigned to the regimen started adjuvant therapy, and fewer than one-third completed the planned 9 cycles of enfortumab vedotin and 17 cycles of pembrolizumab. In the control arm, 34 of 174 patients received adjuvant therapy, including 29 who received adjuvant nivolumab.¹

The model did not include patient out-of-pocket expenses or indirect and societal costs, and the findings may not apply to other payers or countries. Because long-term treatment-related complications were not reported in the trial, toxic effects were modeled as acute events, which may underestimate the effects of persistent toxicities such as immune-related adverse events. The authors called for budget impact analyses to evaluate the financial consequences for payers.

The authors concluded that the findings support the regimen as a “clinically valuable and economically reasonable standard treatment” for cisplatin-ineligible MIBC, noting that variability in cost-effectiveness was identified in sensitivity analyses.¹

REFERENCES

1. Su ZT, Garman TS, Rivera Lopez CA, et al. Cost-effectiveness of perioperative enfortumab vedotin and pembrolizumab for bladder cancer. JAMA Netw Open. 2026;9(10):e2640370. doi:10.1001/jamanetworkopen.2026.40370

2. Vulsteke C, Adra N, Danchaivijitr P, et al. Perioperative enfortumab vedotin and pembrolizumab in bladder cancer. N Engl J Med. 2026;394(13):1257-1269. doi:10.1056/NEJMoa2511674

3. FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. US FDA. November 21, 2025. Accessed November 4, 2026. https://tinyurl.com/3p3mfhvb

4. FDA approves pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph each with enfortumab vedotin-ejfv for muscle invasive bladder cancer. US FDA. July 10, 2026. Accessed November 4, 2026. https://tinyurl.com/46k3k7pe