Imfinzi (durvalumab )perioperative regimen reduced the risk of recurrence by 32% and the risk of death by 25% vs. neoadjuvant chemotherapy alone in muscle-invasive bladder cancer in the NIAGARA phase III trial

Patients were treated with Imfinzi in combination with neoadjuvant chemotherapy before radical cystectomy (surgery to remove the bladder) followed by Imfinzi as adjuvant monotherapy. These results will be presented during a Presidential Symposium at the 2024 European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain (abstract #LBA5) and simultaneously published in The New England Journal of Medicine.

In a planned interim analysis, patients treated with the Imfinzi perioperative regimen showed a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death versus the comparator arm (based on 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 Imfinzi regimen were event free at two years compared to 59.8% in the comparator arm.

Results from the key secondary endpoint of OS showed the Imfinzi perioperative regimen reduced the risk of death by 25% versus neoadjuvant chemotherapy with radical cystectomy (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 Imfinzi regimen were alive at two years compared to 75.2% in the comparator arm.

Professor Thomas Powles, MD, Director of Barts Cancer Centre (QMUL), London, UK, and principal investigator in the NIAGARA trial, said: “Neoadjuvant chemotherapy with bladder removal has been the mainstay of treatment for patients with muscle-invasive bladder cancer for nearly twenty years; however, half of patients still go on to suffer a devastating recurrence. Adding durvalumab before and after surgery significantly reduced the chance of recurrence and extended survival, a significant advance with the potential to transform the standard of care for these patients who desperately need better outcomes.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The NIAGARA data showed compelling improvements in both event-free survival and overall survival, with more than 80 per cent of patients treated with the Imfinzi perioperative regimen alive at two years. This is the first immunotherapy regimen to significantly extend overall survival in muscle-invasive bladder cancer, and it further validates our strategy to move cancer treatment as early as possible to maximise benefit for patients.”

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. Grade 3 and 4 adverse events due to any cause occurred in 69% of patients treated with Imfinzi and 68% of patients treated with neoadjuvant chemotherapy.

In addition to NIAGARA, Imfinzi is also being tested across early- and late-stage bladder cancer in various treatment combinations, including in non-muscle invasive disease (POTOMAC), patients with MIBC who are cisplatin-ineligible or refusing cisplatin (VOLGA) and locally advanced or metastatic disease (NILE).

Citation:"Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer ";Authors: Thomas Powles, M.D., James W.F. Catto, Ph.D., F.R.C.S.(Urol.), Matthew D. Galsky, M.D., Hikmat Al-Ahmadie, M.D. , Joshua J. Meeks, M.D., Ph.D., Hiroyuki Nishiyama, M.D., Ph.D., Toan Quang Vu, M.D., +18, for the NIAGARA Investigators. NEJM.Published September 15, 2024.