European Commission approves perioperative pembrolizumab plus enfortumab vedotin for MIBC

The European Commission has approved pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) each in combination with enfortumab vedotin-ejfv (Padcev) as perioperative regimens for adult patients with muscle invasive bladder cancer (MIBC) who are candidates for cystectomy.¹

This approval extends the perioperative use of EV plus pembrolizumab—or its subcutaneous formulation pembrolizumab and berahyaluronidase alfa-pmph— to all patients with MIBC, regardless of cisplatin eligibility, building on the June 2026 approval of the combination for cisplatin-ineligible MIBC.

“Although cisplatin-based chemotherapy has been a standard treatment approach for many patients with muscle-invasive bladder cancer, recurrence remains a significant challenge,” said Dr. Alfonso Gómez de Liaño Lista, Hospital Universitario Insular de Gran Canaria, and KEYNOTE-B15 primary investigator, in a news release on the approval.¹ “Based on results from the KEYNOTE-B15 trial, today’s approval is a meaningful advance for patients with muscle-invasive bladder cancer in the European Union, extending this chemotherapy-free perioperative treatment option to patients regardless of cisplatin eligibility.”

Data on pembrolizumab plus enfortumab vedotin

The approval is supported by results from the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124), which demonstrated that the combination led to significant improvements in event-free survival (EFS), overall survival (OS), and pathological complete response (pCR) rate vs neoadjuvant cisplatin-gemcitabine in patients with MIBC who are eligible for cisplatin-based chemotherapy. These findings have been published in the New England Journal of Medicine.²

The trial enrolled 808 patients with histologically confirmed MIBC who were randomly assigned 1:1 to receive perioperative EV plus pembrolizumab and radical cystectomy with pelvic lymph node dissection (n = 405), or to standard neoadjuvant gemcitabine plus cisplatin (n = 403) followed by surgery. The experimental arm received 4 neoadjuvant cycles of EV plus pembrolizumab, followed by 5 adjuvant cycles of EV and 13 adjuvant cycles of pembrolizumab. The control arm underwent observation after surgery.

The trial met its primary end point of EFS. Median EFS was not reached in the EV/pembrolizumab arm vs 48.5 months in the gemcitabine/cisplatin arm (HR, 0.53; 95% CI, 0.41 to 0.70; P < .0001). At 2 years, the estimated EFS rate was 79.4% with EV/pembrolizumab vs 66.2% in the control arm. Overall survival (OS) was also significantly improved, with a 35% reduction in the risk of death (HR, 0.65; 95% CI, 0.48 to 0.89; P = .0029) and a 24-month estimated OS rate of 86.9% in the EV/pembrolizumab arm vs 81.3% in the control arm.

The pathologic complete response (pCR) rate at surgery was 55.8% with EV/pembrolizumab vs 32.5% with gemcitabine/cisplatin—a difference of 23.4 percentage points (95% CI, 16.7 to 29.8; P < .0001). Further, 2-year disease-free survival per Kaplan–Meier estimate was 86.1% in the EV/pembrolizumab arm and 72.6% in the control arm (HR, 0.50; 95% CI, 0.36 to 0.70).

Grade 3 or higher adverse events (AEs) of any cause occurred in 75.7% of patients in the EV/pembrolizumab arm vs 67.2% in the gemcitabine/cisplatin arm, with 2 treatment-related deaths in the experimental arm and 1 in the control arm. The most common treatment-related AEs of special interest with enfortumab vedotin included skin reactions (63.5%) and peripheral neuropathy (36.0%). The most common AEs of special interest with pembrolizumab were severe skin reactions (17.1%) and hypothyroidism (12.2%).

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REFERENCES

1. European Commission approves KEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab vedotin-ejfv) as perioperative treatment for adults with resectable muscle-invasive bladder cancer (MIBC). News release. Merck. October 21, 2026. Accessed October 21, 2026. https://www.businesswire.com/news/home/20261021594617/en/European-Commission-Approves-KEYTRUDA-pembrolizumab-Plus-Padcev-enfortumab-vedotin-ejfv-as-Perioperative-Treatment-for-Adults-With-Resectable-Muscle-Invasive-Bladder-Cancer-MIBC

2. Galsky MD, Valderrama BP, Maruzzo M, et al. Enfortumab vedotin and pembrolizumab in cisplatin-eligible bladder cancer. N Engl J Med. 2026;395:338-348. doi:10.1056/NEJMoa2601486