Data from the phase 3 NIAGARA study indicates that perioperative durvalumab (Imfinzi) combined with neoadjuvant chemotherapy, followed by radical cystectomy and adjuvant durvalumab, significantly improves event-free survival (EFS) and overall survival (OS) in patients with cisplatin-eligible muscle-invasive bladder cancer (MIBC). The findings, presented at the 2024 European Society for Medical Oncology (ESMO) Congress and published in The New England Journal of Medicine, suggest a potential new standard of care for this patient population.
Study Design and Patient Population
The NIAGARA trial (NCT03732677) enrolled 1530 patients, with 1063 randomized 1:1 to either the durvalumab arm or the comparator arm. Eligible patients had cisplatin-eligible MIBC (cT2-T4aN0/1M0), urothelial cancer or urothelial cancer with divergent differentiation or histologic subtypes, were evaluated and confirmed for radical cystectomy, and had a creatine clearance of 40 mL/min or lower. The durvalumab arm received neoadjuvant durvalumab (1500 mg intravenously Q3W) plus gemcitabine and cisplatin for 4 cycles, followed by radical cystectomy and 8 cycles of adjuvant durvalumab. The comparator arm received 4 cycles of gemcitabine plus cisplatin followed by radical cystectomy. The dual primary endpoints were EFS and pathological complete response (pCR).
Efficacy Results
The study demonstrated a significant reduction in the risk of an event in the durvalumab arm (HR=0.68, 95% CI, 0.56-0.82). With a median follow-up of 42.3 months (range 0.03-61.3 months), the 2-year landmark EFS was 68% in the durvalumab arm compared to 60% in the comparator arm, representing an 8% improvement. Overall survival also showed a statistically significant 25% reduction in the risk of death in the durvalumab arm (HR=0.75, 95% CI, 0.59-0.93, P = .0106), with 136 deaths (25.5%) in the durvalumab arm versus 169 deaths (31.9%) in the comparator arm.
Safety Profile
The adverse event (AE) profiles were similar between the two arms. Grade 3 or 4 AEs occurred in 69% of patients in the durvalumab arm and 68% in the comparator arm. Grade 3 or 4 treatment-related AEs occurred in 41% of patients in both arms. Discontinuation of neoadjuvant chemotherapy due to AEs occurred in 14% of patients in the durvalumab arm and 15% in the comparator arm.
Expert Commentary
According to Thomas B. Powles, MBBS, MRCP, MD, director of the Barts Cancer Centre at St. Bartholomew’s Hospital in London, the NIAGARA trial represents a significant advancement in the treatment of muscle-invasive bladder cancer. "NIAGARA supports perioperative durvalumab with neoadjuvant chemotherapy as a potential new standard treatment for patients with cisplatin-eligible muscle-invasive bladder cancer."
