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Bladder Cancer · Medical Oncology · Evidence review 2026-10-14

EV-304 / KEYNOTE-B15

For cisplatin-eligible patients with operable MIBC, does perioperative enfortumab vedotin plus pembrolizumab improve EFS and OS versus neoadjuvant gemcitabine–cisplatin and cystectomy?

Population
808 cisplatin-eligible patients with previously untreated MIBC who were candidates for radical cystectomy and pelvic lymph-node dissection.
Experimental treatment
Four neoadjuvant cycles of enfortumab vedotin 1.25 mg/kg on days 1 and 8 plus pembrolizumab 200 mg every 3 weeks, followed by cystectomy and adjuvant EV plus pembrolizumab.
Comparator
Four cycles of neoadjuvant gemcitabine–cisplatin followed by cystectomy.
Study design
Phase III randomized trial

Key reported outcomes

Values are reproduced from the linked sources. Bars are a visual aid and are scaled within each outcome row; do not compare bar lengths across different endpoints.

Median event-free survival

Not reached with perioperative EV–pembrolizumab versus 48.5 months with gemcitabine–cisplatin. No bar is shown because a not-reached median is not a numeric value.

EFS hazard ratio
Treatment
0.53
Comparator
1.00
Overall-survival hazard ratio
Treatment
0.65
Comparator
1.00

Median EFS was not reached with perioperative EV–pembrolizumab versus 48.5 months with gemcitabine–cisplatin (HR 0.53, 95% CI 0.41–0.70; P<0.0001). OS also favoured EV–pembrolizumab (HR 0.65, 95% CI 0.48–0.89; P=0.0029).

Critical appraisal

This is a perioperative strategy comparison, not a direct comparison with NIAGARA or a trial of EV–pembrolizumab versus adjuvant-only immunotherapy. Follow the paper's endpoint definitions; do not convert hazard ratios into NNT.

Absolute-effect discipline: NNT/NNH is not calculated unless a defensible absolute difference and a common time horizon are available. Median survival differences and hazard ratios alone are not converted into NNT.

Current-practice context

Reviewed 2026-10-14; this is a dated evidence-context note, not a substitute for local guidelines or individual clinical judgement.

The FDA expanded the perioperative EV–pembrolizumab indication to cisplatin-eligible MIBC on 10 July 2026. Treatment selection should account for EV-associated neuropathy, rash and hyperglycaemia, immune toxicity, and patient fitness.

Freshness status: this page has a dated context and source links, but is not a claim that every relevant guideline or subsequent publication has been exhaustively reviewed.

Sources