FDA Approves Perioperative Durvalumab Plus Chemo for Muscle-Invasive Bladder Cancer

FDA

The FDA has approved durvalumab (Imfinzi) with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment after radical cystectomy, for adult patients with muscle-invasive bladder cancer.¹

The regulatory decision was supported by data from the phase 3 NIAGARA trial (NCT03732677). Findings showed that patients treated in the durvalumab arm experienced a median event-free survival (EFS) that was not reached (NR; 95% CI, NR-NR) compared with 46.1 months (95% CI, 32.2-NR) for neoadjuvant chemotherapy alone (HR, 0.68; 95% CI, 0.56-0.82; 2-sided P < .0001).

The median overall survival (OS) was not reached in either arm (HR, 0.75; 95% CI, 0.59-0.93; 2-sided P = .0106).

The global, randomized, open-label NIAGARA trial enrolled 1063 patients with MIBC who had not received prior systemic therapy for bladder cancer and were eligible for radical cystectomy. Patients needed to have an ECOG performance status (PS) of 0 or 1, and a creatinine clearance (CrCl) of at least 40 mL/min.²

Patients were randomly assigned in a 1:1 fashion to receive either neoadjuvant durvalumab plus gemcitabine/cisplatin followed by adjuvant durvalumab; or neoadjuvant gemcitabine/cisplatin alone followed by observation post-surgery. Durvalumab was given at 1500 mg once every 3 weeks for 4 cycles in the neoadjuvant setting, then once every 4 weeks after radical cystectomy for 8 cycles. In both arms, gemcitabine and cisplatin were given once every 3 weeks for 4 cycles prior to cystectomy.

Patients were stratified according to clinical tumor stage (T2N0 vs >T2N0), renal function (CrCl ≥ 60 mL/min vs ≥40 to <60 mL/min), and PD-L1 status (high vs low or negative expression).

The primary end point was EFS by investigator assessment. Secondary end points included OS, pathological complete response rate, bladder-intact EFS, and safety.

Additional data presented at the 2024 ESMO Congress showed that durvalumab generated a pCR rate of 33.8% (95% CI, 29.8%-38.0%) vs 25.8% (95% CI, 22.2%-29.8%) for the control arm (odds ratio [OR], 1.49; 95% CI, 1.14-1.96; P = .0038); notably, the pCR difference did not meet the threshold for significance (P = .001).

Regarding safety, the profile of durvalumab in combination with gemcitabine and cisplatin was consistent with previous reports. Rates of grade 3 or higher adverse effects were comparable between the study arms with no new safety signals identified.¹

References

1. FDA approves durvalumab for muscle invasive bladder cancer. FDA. March 28, 2025. Accessed March 28, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-muscle-invasive-bladder-cancer
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). Ann Oncol. 2024;35(suppl 2):S1271. doi:10.1016/j.annonc.2024.08.2327