Perioperative EV-Pembrolizumab Likely to be Cost-Effective and Extend Survival in Cisplatin-Ineligible MIBC

Adding perioperative enfortumab vedotin plus pembrolizumab to radical cystectomy for cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) was projected to extend survival and was likely cost-effective compared with cystectomy alone, according to an economic evaluation published in JAMA Network Open.

The investigators noted that nearly half of patients with localized MIBC are ineligible for cisplatin-based neoadjuvant chemotherapy and have historically proceeded to cystectomy without it. In the phase 3 KEYNOTE-905/EV-303 trial, the perioperative combination improved event-free and overall survival vs cystectomy alone, but moving it into the curative setting may increase upfront costs for a large population, they wrote.

The researchers built a decision-analytic Markov model informed by KEYNOTE-905/EV-303 data, simulating 10,000 patients aged 73 years from a US Medicare payer perspective over 10 years. Compared with cystectomy alone, the combination increased projected survival from 4.12 to 5.63 life-years and from 3.20 to 4.51 quality-adjusted life-years (QALYs) per patient and raised total costs from $317,513 to $412,160. Higher upfront treatment costs were partially offset by lower postprogression treatment costs ($12,578 vs $238,729 per patient) . The incremental cost-effectiveness ratio was $72,460 per QALY, below a willingness-to-pay threshold of $100,000 per QALY.

The result was sensitive to key assumptions. The ratio rose to $229,658 per QALY with a 5-year horizon and to $151,046 per QALY when all patients undergoing cystectomy were assumed to start adjuvant therapy, both above the threshold, and fell to $59,218 per QALY over a lifetime horizon. In probabilistic sensitivity analysis, the combination had a 53% probability of being cost-effective at the $100,000 threshold.

The authors noted that the model extrapolated survival beyond the trial's follow-up, modeled toxic effects as acute events that may underestimate persistent immune-related effects, excluded out-of-pocket and indirect costs, and may not generalize beyond the US Medicare perspective. They said the results should be validated as longer-term clinical data become available.

Source: 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