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

EV-303 / KEYNOTE-905

For cisplatin-ineligible or cisplatin-declining patients with operable MIBC, does perioperative enfortumab vedotin plus pembrolizumab improve outcomes over immediate cystectomy?

Population
344 patients with previously untreated MIBC who were candidates for radical cystectomy and ineligible for or declined cisplatin-based chemotherapy.
Experimental treatment
Three neoadjuvant cycles of enfortumab vedotin 1.25 mg/kg on days 1 and 8 plus pembrolizumab 200 mg every 3 weeks, then cystectomy; adjuvant EV plus pembrolizumab followed by pembrolizumab monotherapy.
Comparator
Immediate radical cystectomy with pelvic lymph-node dissection.
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.

2-year event-free survival
Treatment
74.7%
Comparator
39.4%
2-year overall survival
Treatment
79.7%
Comparator
63.1%
Pathological complete response
Treatment
57.1%
Comparator
8.6%

At the reported analysis, 2-year EFS was 74.7% versus 39.4% and 2-year OS was 79.7% versus 63.1%; pCR was 57.1% versus 8.6%. EFS HR 0.40 (95% CI 0.28–0.57); OS HR 0.50 (95% CI 0.33–0.74).

Critical appraisal

Open-label phase III trial; treatment adds substantial systemic toxicity and requires perioperative EV and pembrolizumab. pCR is not a substitute for long-term survival. Discuss surgical fitness, neuropathy, rash, hyperglycaemia and immune-mediated toxicity.

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.

US FDA approval was granted in November 2025 for cisplatin-ineligible MIBC candidates for cystectomy. The 2026 evidence atlas should distinguish this perioperative regimen from NIAGARA's cisplatin-based perioperative durvalumab strategy and from EV-304 in cisplatin-eligible patients.

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