Perioperative Durvalumab Plus Chemo Meets EFS, OS End Points in MIBC

Treatment with neoadjuvant durvalumab (Imfinzi) in combination with gemcitabine and cisplatin, followed by adjuvant durvalumab monotherapy after cystectomy, demonstrated statistically significant and clinically meaningful improvement in event-free survival (EFS) and overall survival (OS) vs neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC), meeting the primary end point of EFS and the key secondary end point of OS in the phase 3 NIAGARA trial (NCT03732677).¹

According to an announcement from AstraZeneca, the NIAGARA treatment regimen is the first immunotherapy perioperative regimen to extend survival in bladder cancer.

Durvalumab was reported to be generally well-tolerated, with no new safety concerns observed in both the neoadjuvant and adjuvant settings, and the safety profile of the agent combined with neoadjuvant chemotherapy aligned with the known profiles of the individual medications. Additionally, the addition of durvalumab to treatment did not increase the discontinuation rate due to adverse effects or hinder patients' ability to undergo surgery compared with the use of neoadjuvant chemotherapy alone.

These data will be presented at an upcoming medical meeting and shared with global regulatory authorities.

“Nearly half of patients with MIBC who receive standard of care still experience disease recurrence or progression. These NIAGARA data show for the first time that adding durvalumab to chemotherapy before surgery followed by durvalumab extends patients’ lives,” trial investigator Thomas Powles, MD, professor and director of Barts Cancer Centre (QMUL), in London, United Kingdom, stated in a news release.

The randomized, open-label, multi-center, global NIAGARA trial enrolled 1063 patients to receive durvalumab plus chemotherapy or chemotherapy alone prior to cystectomy, followed by durvalumab or no further treatment after cystectomy.

Patients were required to have resectable MIBC with a clinical stage of T2-T4aN0/1M0 with transitional and mixed transitional cell histology who were planning to undergo radical cystectomy and had not received prior systemic chemotherapy or immunotherapy for MIBC. Additional eligibility criteria included an ECOG performance status of 0 or 1, along with a life expectancy of at least 12 weeks at randomization.²

Patients were excluded from the trial if they had evidence of lymph node (N2-N3) or metastatic (M1) disease at screening; received prior pelvic radiotherapy within 2 years of randomization; or had previous exposure to immune-mediated therapies (excluding Bacillus Calmette-Guérin). Current or prior use of immunosuppressive medication within 14 days prior to the first dose of the investigational product was not allowed.

NIAGARA was conducted at 192 centers across 22 countries and regions, including North America, South America, Europe, Australia, and Asia.¹

The dual primary end points of the investigation were EFS and pathologic complete response rate at the time of cystectomy. Along with OS and safety, other secondary end points included EFS at 24 months, the proportion of patients who underwent cystectomy, time to second progression, metastasis-free survival, disease-specific survival, and disease-free survival.²

“The NIAGARA results support our strategy to move immunotherapy to the early stages of cancer treatment. This perioperative regimen with [durvalumab] improved survival and reduced the rate at which patients experience disease recurrence or progression,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, added in a news release.¹ “We are eager to bring this regimen with the potential to transform the standard of care to patients as soon as possible.”

References

1. Imfinzi demonstrated statistically significant and clinically meaningful improvement in event-free survival and overall survival for muscle-invasive bladder cancer in NIAGARA phase III trial. News release. AstraZeneca. June 25, 2024. Accessed June 25, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-improved-efs-and-os-in-bladder-cancer.html
2. Durvalumab+ gemcitabine/cisplatin (neoadjuvant treatment) and durvalumab (adjuvant treatment) in patients with MIBC (NIAGARA). ClinicalTrials.gov. Updated March 18, 2024. Accessed June 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03732677