Systematic review and meta-analysis of 15 prospective Phase II+ trials (n=1,545) comparing pathological complete response (pCR: ypT0N0) and survival outcomes among neoadjuvant enfortumab vedotin (EV) monotherapy, EV plus pembrolizumab (EV+P), and ICI-based regimens for muscle-invasive bladder cancer (MIBC); studies published January 2015–October 2025.
Pooled pCR was highest for EV+P at 57% (95% CI 49%–65%), versus 37% (34%–39%) for ICI-based regimens (13 studies, n=1,353) and 36% (17%–59%) for EV monotherapy (n=22); EV+P significantly outperformed ICI-based regimens (P<.0001). In cisplatin-ineligible patients, EV+P pCR (57%) exceeded ICI-based pCR (29%). Pooled radical cystectomy completion was 89%. From EV-303, EV+P vs. surgery alone yielded EFS HR 0.40 (0.28–0.57) and OS HR 0.50 (0.33–0.74).
- EV+P data largely driven by a single trial (EV-303), limiting inference across the pooled estimate. - Survival HRs (EFS/OS) could not be pooled due to different comparators across trials. - Indirect comparisons only; no head-to-head RCT between EV+P and ICI-based neoadjuvant regimens exists.
For cisplatin-ineligible MIBC patients, neoadjuvant EV+P achieves a substantially higher pCR (~57%) than ICI-based regimens (~29%) with comparable surgical completion (~89%); combined with EFS and OS benefits from EV-303, EV+P should be considered a leading perioperative option in this population.
Explore related topics
