AstraZeneca's Imfinzi (durvalumab) has received priority review from the U.S. Food and Drug Administration (FDA) for the treatment of muscle-invasive bladder cancer (MIBC). This action accelerates the review process for the supplemental Biologics License Application (sBLA), with a decision expected in the second quarter of 2025. The sBLA is based on the Phase III NIAGARA trial, which demonstrated significant improvements in event-free survival (EFS) and overall survival (OS) with the use of perioperative durvalumab.
MIBC is a form of bladder cancer where the tumor has invaded the muscle wall of the bladder. It accounts for approximately one in four bladder cancer diagnoses. The current standard of care involves neoadjuvant chemotherapy followed by radical cystectomy, but nearly half of patients experience disease recurrence, highlighting the urgent need for new treatment options.
The NIAGARA trial (NCT03732677) is a randomized, open-label, multi-center, global Phase III trial evaluating perioperative IMFINZI as treatment for patients with MIBC before and after radical cystectomy. In the trial, 1,063 patients were randomized to receive IMFINZI plus neoadjuvant chemotherapy prior to cystectomy followed by IMFINZI, or neoadjuvant chemotherapy alone prior to cystectomy with no further treatment after surgery. NIAGARA is the largest global Phase III trial in this setting.
NIAGARA Trial Results
The NIAGARA trial enrolled adult patients with cisplatin-eligible MIBC. Patients received either neoadjuvant durvalumab plus gemcitabine and cisplatin, followed by radical cystectomy and adjuvant durvalumab, or gemcitabine and cisplatin alone followed by radical cystectomy. The dual primary endpoints were EFS and pathological complete response (pCR).
Results from the trial, presented at the 2024 European Society for Medical Oncology (ESMO) Congress, showed a 32% reduction in the risk of disease progression, recurrence, or death with the durvalumab regimen (HR=0.68, 95% CI, 0.56-0.82, P<0.0001). At two years, 67.8% of patients treated with durvalumab were event-free, compared to 59.8% in the comparator arm.
Overall Survival Benefit
The study also demonstrated a 25% reduction in the risk of death with the durvalumab perioperative regimen (HR=0.75, 95% CI 0.59-0.93, P = 0.0106). The two-year overall survival rate was 82.2% in the durvalumab arm, compared to 75.2% in the comparator arm.
Safety and Tolerability
Durvalumab was generally well-tolerated, with no new safety signals observed. Grade 3 or 4 adverse events occurred in 69% of patients in the durvalumab arm and 68% in the comparator arm. Treatment-related adverse events leading to discontinuation occurred in 14% of patients in the durvalumab arm and 15% in the comparator arm.
Expert Commentary
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, stated, "New options for muscle-invasive bladder cancer are vital because nearly half of patients will see their cancer return or progress despite undergoing curative-intent treatment, including removal of their bladder. Today’s Priority Review designation recognizes the urgent need for new options for these patients and the potential of Imfinzi to transform the standard of care as the first and only perioperative immunotherapy regimen to delay recurrence and extend survival in this setting."
Implications for Clinical Practice
If approved, durvalumab could become a transformative option for MIBC patients, offering a perioperative immunotherapy regimen that significantly improves event-free and overall survival. Regulatory applications are also under review in the EU, Japan, and several other countries.
