Imfinzi Plus Chemo Shows Statistically Significant Event-Free Survival Improvement Treating Muscle-Invasive Bladder Cancer

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Data from the Phase III NIAGARA trial (NCT03732677)found that Imfinzi (durvalumab; AstraZeneca) combined with chemotherapy produced a statistically significant and clinically meaningful improvement in one of the trial’s dual primary endpoints of event-free survival (EFS) and for the key secondary endpoint of overall survival (OS) compared with neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC).¹ Imfinzi is a human immunoglobulin G1 kappa monoclonal antibody that attaches to PD-L1 to block the interaction of PD-L1 with PD-1 and CD80.²

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

Current FDA-approved indications for Imfinzi include for the treatment of unresectable, stage III non-small cell lung cancer (NSCLC) in patients with disease that has not progressed following chemoradiation therapy; for the treatment of extensive-stage small cell lung cancer; combined with a limited course of Imjudo (tremelimumab) and chemotherapy to treat metastatic NSCLC; in combination with gemcitabine plus cisplatin to treat locally advanced or metastatic biliary tract cancer; and in combination with Imjudo to treat unresectable hepatocellular carcinoma.

The randomized, open-label, multicenter, global, NIAGARA trial evaluated the efficacy and safety of Imfinzi in patients with MIBC prior to and following radical cystectomy. Investigators randomly assigned 1063 patients to receive Imfinzi combined with chemotherapy or to receive chemotherapy alone prior to cystectomy followed by Imfinzi or no additional therapy post-surgery.³

Enrollment criteria included patients with resectable MIBC with clinical stage T2 to T4aN0/1M0 with transitional and mixed transitional cell histology who had planned to undergo radical cystectomy and who were not previously treated with systemic chemotherapy or immunotherapy for MIBC; ECOG performance status of 0 or 1; and life expectancy of at least 12 weeks at randomization. Along with EFS, the trial’s other primary endpoint was pathologic complete response, with OS and safety among the trial’s key secondary endpoints.

In terms of safety, Imfinzi was generally well-tolerated with no new signals reported in both the neoadjuvant and adjuvant setting. The safety profile of Imfinzi and neoadjuvant chemotherapy was similar to prior reports for each individual agent. Investigators reported that the addition of Imfinzi to chemotherapy did not result in an increased discontinuation rate because of adverse events and did not impact the ability to complete surgery compared to treatment with neoadjuvant chemotherapy alone. Data from the trial will be presented at an upcoming medical meeting and submitted to global regulatory authorities.

“Nearly half of patients with muscle-invasive bladder cancer who receive standard of care still experience disease recurrence or progression,” trial investigator professor Thomas Powles, MD, professor, director of Barts Cancer Centre, London, UK, said in the release. “These NIAGARA data show for the first time that adding durvalumab to chemotherapy before surgery followed by durvalumab extends patients’ lives.”¹

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. Imfinzi Full Prescribing Information (den8dhaj6zs0e.cloudfront.net)

3. 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://clinicaltrials.gov/study/NCT03732677