FDA Approves Perioperative Durvalumab Plus Chemotherapy for MIBC

Adverse effects were consistent with previous findings on durvalumab with platinum-based chemotherapy.

The FDA approved neoadjuvant therapy with durvalumab (Imfinzi) for use with gemcitabine and cisplatin, followed by adjuvant durvalumab monotherapy after radical cystectomy in adults with muscle invasive bladder cancer (MIBC).¹

The combination’s efficacy was shown in the randomized, open-label, multicenter phase 3 trial NIAGARA (NCT03732677), in which 1,063 patients were randomized 1:1 to treatment with neoadjuvant durvalumab plus chemotherapy followed by adjuvant durvalumab after surgery or neoadjuvant chemotherapy followed by surgery.¹

Safety and Dosage

Adverse effects (AEs) were consistent with previous experience with durvalumab plus platinum-based chemotherapy.¹

The combination has a recommended dose of 1,500 mg of durvalumab every 3 weeks with chemotherapy during neoadjuvant treatment and 1,500 mg of durvalumab monotherapy every 4 weeks in the adjuvant setting for patients with a body weight greater than or equal to 30 kg. Treatment is recommended until patients experience unacceptable toxicity, recurrence, or disease progression that prevents definitive surgery.¹

Efficacy

Event-free survival (EFS) and overall survival (OS), primary and secondary end points, respectively, of NIAGRA, were statistically significantly improved by the combination therapy.

Median EFS was not reached (NR) in the durvalumab plus chemotherapy arm (95% CI, NR-NR) vs 46.1 months (95% CI, 32.2-NR) in the chemotherapy arm (hazard ratio [HR], 0.68; 95% CI, 0.56-0.82; two-sided P < .0001). Median OS was NR in both arms (HR, 0.75; 95% CI, 0.59-0.93; two-sided P = .0106).

Safety in Prior Analyses

Previously reported results from a pre-planned interim analysis of NIAGARA that compared the above treatment with durvalumab and chemotherapy to placebo indicated that the combination indicated no new safety signals.

Most patients in both arms of the trial experienced AEs of any cause (99% in the durvalumab arm; 100% in the comparator arm), of which 69% and 68%, respectively, were grade 3 or 4. Serious AEs occurred in 62% and 55% of patients, respectively.²

AEs that led to death (5%; 6%), discontinuation of study treatment (21%; 15%), discontinuation of neoadjuvant durvalumab (9%; not applicable [NA]), discontinuation of neoadjuvant chemotherapy (14%; 15%), not undergoing radical cystectomy (1%; 1%), delayed surgery (2%; 1%), and discontinuation of adjuvant durvalumab (8%; NA) occurred.²

In both arms, 41% of patients had potentially treatment-related AEs (TRAEs). Of those, 0.6% resulted in death in both arms. Immune-mediated AEs of any grade were reported in 21% of patients taking durvalumab and 3% of patients in the chemotherapy arm. In the adjuvant phase, potential TRAEs were seen in 41% and 6% of patients in the durvalumab and placebo arms, respectively; 6% and 1% of these were grade 3/4. No potential adjuvant TRAEs led to death in either arm.²

The most common any-grade AEs were nausea (durvalumab arm, 54%; placebo arm, 49%), anemia (39%; 41%), constipation (39%; 39%), fatigue (36%; 32%), urinary tract infection (30%; 29%), decreased appetite (27%; 25%), neutropenia (26%; 31%), pyrexia (21%; 17%), diarrhea (21%; 14%), vomiting (19%; 18%), blood creatinine increase (19%; 15%), asthenia (18%; 18%), neutrophil count decrease (15%; 14%), and pruritis (15%; 7%).¹

Reference

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). Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA5.