FDA Grants Approval to Durvalumab in MIBC

US FDA

• Durvalumab (Imfinzi) has been approved by the FDA for the treatment of patients with muscle-invasive bladder cancer (MIBC).
• Positive data from the phase 3 NIAGARA trial (NCT03732677) support this approval.
• In the study, durvalumab led to statistically significant and clinically meaningful improvements in event-free survival (EFS) and overall survival (OS) in this patient population.

The FDA has approved durvalumab plus chemotherapy followed by single-agent durvalumab for the treatment of patients with MIBC after radical cystectomy, based on findings from the phase 3 NIAGARA trial.¹

According to data from the randomized, open-label, multicenter, global NIAGARA trial presented during the 2024 European Society for Medical Oncology (ESMO) Congress and simultaneously published in The New England Journal of Medicine, neoadjuvant durvalumab given with chemotherapy, followed by adjuvant durvalumab, significantly improved EFS and OS in patients with cisplatin-eligible MIBC vs neoadjuvant chemotherapy plus placebo. These benefits were achieved without affecting patients' ability to undergo radical cystectomy.

This approval of durvalumab for patients with MIBS marks the first and only perioperative immunotherapy regimen available for this patient population.

The NIAGARA trial included adult patients with cisplatin-eligible MIBC with a clinical stage of T2-T4aN0/1M0.2 A total of 1530 patients were enrolled in the study, and 1063 patients were randomly assigned in a 1:1 fashion to receive 1500 mg of intravenous durvalumab every 3 weeks plus gemcitabine/cisplatin for 4 cycles, followed by durvalumab alone every 4 weeks post-radical cystectomy for 8 cycles; or 4 cycles of gemcitabine/cisplatin alone prior to cystectomy, followed by no further treatment after surgery.

The primary end points of the trial were EFS by blinded independent review and pCR rate at the time of cystectomy. Secondary end points included OS and safety, and additional end points were disease-free survival, disease-specific survival, metastasis-free survival, health-related quality of life, and 5-year OS.

Findings from the planned interim analysis showed that perioperative durvalumab led to a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death compared with neoadjuvant chemotherapy with radical cystectomy alone (95% CI, 0.56-0.82; P <.0001). Among those treated with durvalumab, the estimated median EFS was not yet reached vs 46.1 months in the comparator arm. At 2 years, an estimated 67.8% of patients in the durvalumab arm vs 59.8% in the comparator arm were event-free.

Looking at OS, treatment with the durvalumab perioperative regimen reduced the risk of death by 25% vs neoadjuvant chemotherapy with radical cystectomy (HR, 0.75; 95% CI, 0.59-0.93; P =.0106). In both arms, the median survival was not yet reached. At 2 years, an estimated 82.2% of patients given the durvalumab regimen and 75.2% in the comparator arm were alive.

The durvalumab regimen was also generally well tolerated with no new safety signals seen in both the neoadjuvant and adjuvant settings. In both arms, the majority of patients had adverse events (AEs) of any cause (99% in the durvalumab arm; 100% in the comparator arm), 69% and 68% of which were grade 3/4, respectively.

Serious AEs were observed in 62% of patients receiving durvalumab and 55% in the comparator arm. Reported AEs included those leading to death (5% vs. 6%), treatment discontinuation (21% vs. 15%), discontinuation of neoadjuvant durvalumab (9%; NA), discontinuation of neoadjuvant chemotherapy (14% vs. 15%), failure to undergo radical cystectomy (1% in both groups), surgical delays (2% vs. 1%), and discontinuation of adjuvant durvalumab (8%; NA).

Additionally, 41% of patients in both arms had potential treatment-related AEs, 0.6% of which resulted in death in both arms. Any-grade immune-mediated AEs were seen in 21% and 3% of patients in the durvalumab arm vs the comparator arm.

REFERENCES

1. FDA approves durvalumab for muscle invasive bladder cancer. News release. FDA. March 28, 2025. Accessed March 28, 2025. https://tinyurl.com/yc57uhb3

2. Powles T, Van der Heijden MS, Galsky M, et al. A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA). Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA5.