Approval based on NIAGARA Phase III trial results which showed a 32% reduction in the risk of recurrence and a 25% reduction in the risk of death for the Imfinzi regimen vs. neoadjuvant chemotherapy alone.
AstraZeneca’s Imfinzi (durvalumab) has been approved in the European Union (EU) for the treatment of adult patients with resectable muscle-invasive bladder cancer (MIBC) in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by Imfinzi as monotherapy adjuvant treatment after radical cystectomy (surgery to remove the bladder).
The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the NIAGARA Phase III trial, which were published in The New England Journal of Medicine.
In a planned interim analysis, the Imfinzi-based perioperative regimen demonstrated a statistically significant 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death versus neoadjuvant chemotherapy with radical cystectomy alone (based on event-free survival [EFS] hazard ratio [HR] of 0.68; 95% confidence interval [CI] 0.56-0.82; p<0.0001). Estimated median EFS was not yet reached for the Imfinzi arm versus 46.1 months for the comparator arm. An estimated 67.8% of patients treated with the regimen were event free at two years compared to 59.8% in the comparator arm.
Results from the key secondary endpoint of overall survival (OS) showed that the Imfinzi-based perioperative regimen reduced the risk of death by 25% versus the comparator arm (based on OS HR of 0.75; 95% CI 0.59-0.93; p=0.0106). Median survival was not yet reached for either arm. An estimated 82.2% of patients treated with the regimen were alive at two years compared to 75.2% in the comparator arm.
In 2024, over 35,000 people in the five major European countries were treated for MIBC.1 Despite this representing a curative-intent setting, many patients experience disease recurrence after surgery with current standard-of-care neoadjuvant chemotherapy.2
Dr Michiel Van der Heijden, medical oncologist and Group Leader at the Netherlands Cancer Institute, and investigator in the NIAGARA trial, said: “The durvalumab-based perioperative regimen is an important new treatment option for patients in Europe with muscle-invasive bladder cancer, as currently nearly half experience disease recurrence despite treatment with neoadjuvant chemotherapy and surgery to remove the bladder. The NIAGARA results showed how this regimen reduced the risk of recurrence by nearly a third and significantly extended survival, underscoring its potential to transform clinical practice in this curative-intent setting.”
Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “Imfinzi is poised to transform the standard of care for muscle-invasive bladder cancer in Europe as the first and only perioperative immunotherapy for these patients. In the NIAGARA Phase III trial, more than 80 per cent of patients were still alive two years after treatment with the Imfinzi regimen, setting a new survival benchmark for a disease that has seen few treatment advances in decades.”
Imfinzi was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery compared to neoadjuvant chemotherapy alone. Immune-mediated adverse events were consistent with the known profile of Imfinzi, manageable and mostly low-grade.
The European Society for Medical Oncology (ESMO) has published its assessment of the NIAGARA regimen against the Magnitude of Clinical Benefit Scale (MCBS), awarding it the highest possible grade of “A” in the curative setting.3 The ESMO-MCBS facilitates improved decision-making regarding the value of anti-cancer therapies and is used in several ways, including in clinical guidelines and in health technology assessments in a growing number of countries.4
Imfinzi is approved in the US and other countries in this setting based on the NIAGARA results. Regulatory applications for this indication are currently under review in Japan and several other countries. Imfinzi is also approved in other curative-intent settings based on the PACIFIC and AEGEAN Phase III trials in non-small cell lung cancer (NSCLC), and in limited-stage small cell lung cancer (SCLC) based on the ADRIATIC Phase III trial.
