AstraZeneca's Imfinzi (durvalumab), when administered before and after surgery in combination with chemotherapy, has demonstrated a statistically significant and clinically meaningful improvement in survival rates for patients with muscle-invasive bladder cancer (MIBC). The Phase III NIAGARA trial results, presented at the European Society for Medical Oncology (ESMO) Congress 2024, indicate a potential shift in how these aggressive bladder tumors are treated.
The NIAGARA trial, a randomized, open-label, multi-center, global Phase III study, involved 1,063 patients with MIBC. Patients were randomized to receive either Imfinzi plus chemotherapy or chemotherapy alone prior to radical cystectomy (surgery to remove the bladder), followed by Imfinzi or no further treatment after surgery. The dual primary endpoints were event-free survival (EFS) and pathologic complete response. Key secondary endpoints included overall survival (OS) and safety.
Significant Improvement in Event-Free and Overall Survival
The Imfinzi perioperative regimen showed a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death (EFS hazard ratio [HR] of 0.68; 95% confidence interval [CI] 0.56-0.82; p<0.0001). The estimated median EFS was not yet reached for the Imfinzi arm versus 46.1 months for the comparator arm. At two years, 67.8% of patients treated with the Imfinzi regimen were event-free compared to 59.8% in the comparator arm.
In terms of overall survival (OS), the Imfinzi perioperative regimen reduced the risk of death by 25% compared to neoadjuvant chemotherapy with radical cystectomy (OS HR of 0.75; 95% CI 0.59-0.93; p=0.0106). Median survival was not yet reached for either arm, but an estimated 82.2% of patients treated with the Imfinzi regimen were alive at two years compared to 75.2% in the comparator arm.
Expert Commentary
Professor Thomas Powles, MD, Director of Barts Cancer Centre (QMUL), London, UK, and principal investigator in the NIAGARA trial, stated, "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."
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, added, "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."
Safety Profile
Imfinzi was generally well tolerated, and no new safety signals were 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 due to any cause occurred in 69% of patients treated with Imfinzi and 68% of patients treated with neoadjuvant chemotherapy.
Ongoing Research
In addition to NIAGARA, Imfinzi is 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).
Implications for Clinical Practice
The NIAGARA trial results suggest that the Imfinzi perioperative regimen could become a new standard of care for patients with MIBC. The improvements in both event-free and overall survival offer a significant advancement over existing treatment options, potentially reducing recurrence rates and extending patients' lives.
