AstraZeneca's IMFINZI® (durvalumab) in combination with chemotherapy has shown promising results in the treatment of muscle-invasive bladder cancer (MIBC). The NIAGARA Phase III trial demonstrated a statistically significant and clinically meaningful improvement in both event-free survival (EFS) and overall survival (OS) compared to neoadjuvant chemotherapy alone. These findings, presented at the 2024 European Society for Medical Oncology (ESMO) Congress and published in The New England Journal of Medicine, suggest a potential shift in the standard of care for MIBC patients.
The NIAGARA trial involved 1,063 patients randomized to receive either durvalumab plus chemotherapy or chemotherapy alone before radical cystectomy, followed by durvalumab or no further treatment after surgery. The primary endpoint was EFS, with OS as a key secondary endpoint.
Significant Improvement in Event-Free Survival
The interim analysis revealed that patients treated with the IMFINZI perioperative regimen experienced a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death (HR 0.68; 95% CI: 0.56-0.82; p<0.0001). The estimated median EFS was not reached in the IMFINZI arm, compared to 46.1 months in the comparator arm. At two years, 67.8% of patients in the IMFINZI arm were event-free, compared to 59.8% in the chemotherapy-only arm.
Overall Survival Benefit
The key secondary endpoint of OS also showed a significant benefit. The IMFINZI perioperative regimen reduced the risk of death by 25% compared to neoadjuvant chemotherapy with radical cystectomy (HR 0.75; 95% CI: 0.59-0.93; p=0.0106). Median survival was not reached for either arm, but the estimated two-year survival rate was 82.2% for the IMFINZI regimen versus 75.2% for the comparator arm.
Expert Commentary
Professor Thomas Powles, MD, Director of Barts Cancer Centre (QMUL), London, UK, and principal investigator in the NIAGARA trial, emphasized the potential impact of these findings: "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 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."
Safety Profile
IMFINZI was generally well-tolerated, with no new safety signals observed in the neoadjuvant and adjuvant settings. The addition of IMFINZI to neoadjuvant chemotherapy did not compromise patients' ability to complete surgery compared to neoadjuvant chemotherapy alone. Grade 3 and 4 adverse events occurred in 69% of patients treated with IMFINZI and 68% of patients treated with neoadjuvant chemotherapy.
Implications for Bladder Cancer Treatment
These results mark a significant advancement in the treatment of MIBC, where approximately 50% of patients experience disease recurrence after cystectomy. The IMFINZI perioperative regimen offers a new strategy to reduce recurrence and improve survival rates in this patient population.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, stated, "The NIAGARA data showed compelling improvements in both event-free survival and overall survival, with more than 80 percent 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 maximize benefit for patients."
