CHMP Recommends EU Approval of Perioperative Durvalumab for Muscle-Invasive Bladder Cancer

Perioperative Durvalumab for Muscle-Invasive

Bladder Cancer | Image Credit: © Sebastian Kaulitzki

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The Committee for Medicinal Products for Human Use of the European Medicines Agency has recommended the approval of perioperative durvalumab (Imfinzi) plus neoadjuvant chemotherapy for the treatment of patients with muscle-invasive bladder cancer (MIBC).1

If approved, durvalumab would be the first perioperative immunotherapy approved for the management of MIBC in the European Union.

This recommendation is based on results from the phase 3 NIAGARA trial (NCT03732677), which evaluated the efficacy and safety of perioperative durvalumab combined with neoadjuvant chemotherapy compared with neoadjuvant chemotherapy alone in patients with cisplatin-eligible MIBC. Previously, these findings led to the March 2025 FDA approval of durvalumab plus gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant therapy for adult patients with MIBC.2

Findings presented during a Presidential Symposium at the 2024 ESMO Congress and concurrently published in The New England Journal of Medicine, demonstrated that at a median follow-up of 42.3 months (range, 0.03-61.3), patients treated with neoadjuvant durvalumab plus gemcitabine and cisplatin, followed by adjuvant durvalumab (n = 533) experienced a median event-free survival (EFS) that was not reached (NR; 95% CI, NR-NR) compared with 46.1 months (95% CI, 32.2-NR) for those given neoadjuvant gemcitabine plus cisplatin alone (n = 530; HR, 0.68; 95% CI, 0.56-0.82; P < .0001).2,3

The 12- and 24-month EFS rates in the durvalumab arm were 76.0% and 67.8%, respectively. These respective rates were 69.9% and 59.8% in the control arm.3 An April 2024 re-analysis of pathologic complete response (pCR) rates showed that patients in the durvalumab arm achieved a pCR rate of 37.3% (95% CI, 33.2%-41.6%) compared with 27.5% (95% CI, 23.8%-31.6%) in the control arm (odds ratio, 1.60; 95% CI, 1.23-2.08; P = .0005)

“Approximately half of patients with MIBC will experience disease recurrence despite curative-intent treatment with neoadjuvant chemotherapy and surgery to remove the bladder. This recommendation for the durvalumab-based perioperative regimen brings us closer to providing an important new treatment option that has demonstrated a significant survival benefit, with the potential to transform the treatment approach for patients across Europe,” Michiel Van der Heijden, MD, PhD, a medical oncologist and group leader at the Netherlands Cancer Institute in Amsterdam, as well as an investigator in the NIAGARA trial, explained in a news release.1

NIAGARA Trial Background and Design

NIAGARA is a randomized, open-label, multicenter, global, phase 3 study designed to evaluate the efficacy and safety of perioperative durvalumab in patients with MIBC undergoing radical cystectomy. According to the news release, this is the largest phase 3 trial conducted to date in the perioperative MIBC setting.

A total of 1063 patients with resectable MIBC were randomly assigned to 1 of 2 treatment arms.3 Patients in the investigational arm received 4 cycles of neoadjuvant durvalumab in combination with platinum-based chemotherapy followed by radical cystectomy and 8 cycles of adjuvant durvalumab monotherapy. Patients in the control arm received neoadjuvant chemotherapy alone followed by radical cystectomy, with no additional systemic treatment administered postoperatively.

The trial is being conducted at 192 sites across 22 countries, spanning North America, South America, Europe, Australia, and Asia.1

NIAGARA’s dual primary end points are EFS (defined as the time from randomization to disease progression, recurrence, failure to undergo cystectomy, or death from any cause) and pCR at the time of cystectomy. Key secondary end points include overall survival and safety, providing a comprehensive evaluation of the clinical benefit and tolerability of the durvalumab-based regimen.

Safety Findings

Durvalumab was generally well tolerated in the NIAGARA trial, with no new safety signals identified in either the neoadjuvant or adjuvant treatment settings. The addition of durvalumab to standard neoadjuvant chemotherapy did not negatively affect patients’ ability to undergo radical cystectomy, and surgical completion rates were comparable between the durvalumab-based and control arms.

The overall safety profile of durvalumab in combination with chemotherapy was consistent with previously reported data. Immune-mediated adverse effects were in line with the established safety profile of durvalumab, predominantly low-grade in severity, and manageable with standard clinical interventions.

“The [durvalumab]-based perioperative regimen in the NIAGARA trial enabled the survival of more than 80% of patients at 2 years after treatment. This supports our strategy of moving our innovative medicines into the earlier stages of disease where the opportunity for treatment with curative intent is greatest. If approved, this novel approach will become a much-needed new treatment option for patients in Europe and could become the new standard of care in this setting,” Susan Galbraith, executive vice president of Oncology Haematology R&D at AstraZeneca, said in the news release.

References

1. Imfinzi recommended for approval in the EU by CHMP as first and only perioperative immunotherapy for muscle-invasive bladder cancer. News Release. AstraZeneca. May 27, 2025. Accessed May 27, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-recommended-in-eu-for-bladder-cancer.html
2. FDA approves durvalumab for muscle invasive bladder cancer. FDA. March 28, 2025. Accessed March 28, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-muscle-invasive-bladder-cancer
3. Powles T, Van der Heijden MS, Galsky M, et al. A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA). Ann Oncol. 2024;35(suppl 2):S1271. doi:10.1016/j.annonc.2024.08.2327