The European Commission has granted Marketing Authorisation for enfortumab vedotin, in combination with pembrolizumab, as neoadjuvant treatment (before surgery) and then continued after radical cystectomy (surgery) as adjuvant treatment, for adults with resectable muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-containing chemotherapy in the European Union (EU).

The approval establishes the first and only approved perioperative (neoadjuvant and adjuvant) treatment option for this patient population in the EU.

The approval is based on results from the Phase 3 EV-303 clinical trial (KEYNOTE-905), in which perioperative enfortumab vedotin plus pembrolizumab significantly improved Event-Free Survival (EFS) and Overall Survival (OS) compared with surgery alone in patients with MIBC who were ineligible for or declined cisplatin-containing chemotherapy.

The combination reduced the risk of tumor recurrence, progression, or death by 60% (Hazard Ratio (HR) 0.40, 95% CI, 0.28-0.57; p<0.0001) and reduced the risk of death by 50% (HR 0.50, 95% CI: 0.33-0.74; p=0.0002).

The safety profile was consistent with the known profiles of the individual medicines, and no new safety signals were observed.

The most common (≥30%) adverse events related to treatment with the combination were pruritus (itching), alopecia, diarrhoea, fatigue, and anaemia.

Results from the trial were recently published in The New England Journal of Medicine.

Moitreyee Chatterjee-Kishore, Ph.D., MBA, Executive Vice President and Head of Oncology Development, Astellas: “For patients with muscle-invasive bladder cancer who are unable to receive cisplatin-based chemotherapy, perioperative treatment options have historically been limited. This approval establishes the first approved perioperative treatment option for these patients in Europe and represents an important advance for patients facing this disease. We remain committed to improving outcomes for people living with bladder cancer through continued innovation across different stages of the disease.”

Christof Vulsteke, M.D., Ph.D., Head of Integrated Cancer Center Ghent (IKG, Belgium) and Clinical Trial Unit Oncology Ghent and EV-303 Principal Investigator: “Despite surgery with curative intent, many patients with muscle-invasive bladder cancer experience disease recurrence. The EV-303 results demonstrated clinically meaningful improvements in both event-free and overall survival, supporting perioperative enfortumab vedotin plus pembrolizumab as an important new treatment option for cisplatin-ineligible patients in Europe.”

Alex Filicevas, Executive Director, World Bladder Cancer Patient Coalition “For patients living with muscle-invasive bladder cancer, the possibility of the cancer returning after surgery can be a source of significant uncertainty and concern for them and their families. But patients who are unable to receive cisplatin-based chemotherapy have historically faced limited treatment options beyond surgery. This approval represents important progress for the bladder cancer community and a significant advance for patients affected by this disease.”

Bladder cancer remains a significant health burden across Europe, with nearly 200,000 people diagnosed each year.

MIBC accounts for up to 30% of all bladder cancer cases.

Up to half of patients with MIBC are ineligible to receive cisplatin-containing chemotherapy.

Until now, there have been no approved perioperative treatment options for these patients, despite a substantial risk of disease recurrence following surgery.

Enfortumab vedotin plus pembrolizumab is already approved in Europe as a first-line treatment for patients with unresectable or metastatic urothelial cancer who are eligible for platinum-containing chemotherapy.

This approval expands the use of the combination into earlier-stage, resectable MIBC for patients who are ineligible for cisplatin-containing chemotherapy, extending its use from advanced disease into a curative-intent treatment setting.

Source: Astellas