NIAGARA Offers Paradigm-Shift for Neoadjuvant Treatment of MIBC

The addition of perioperative durvalumab to neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) offers “meaningful improvement” in event-free survival (EFS) and overall survival (OS) for patients with cisplatin-ineligible muscle invasive bladder cancer (MIBC), according to results of the randomized, phase 3, open-label, multicenter NIAGARA study.

Results were presented by Thomas Powles, MBBS, MRCP, MD, as a late-breaking abstract at the European Society for Medical Oncology Congress 2024.

Current standard-of-care treatment of MIBC for cisplatin-ineligible patients includes NAC followed by RC.

NIAGARA enrolled 1,063 patients with cisplatin-ineligible MIBC and randomized them 1:1 to receive either neoadjuvant durvalumab (1,500 mg IV once every 3 weeks) and NAC (cisplatin plus gemcitabine IV once every 3 weeks) for 4 cycles followed by RC then adjuvant durvalumab monotherapy (1,500 mg IV once every 4 weeks) for eight cycles (durvalumab arm), or NAC followed by RC alone (comparator arm).

Patients were stratified based on clinical tumor stage (cT2N0 disease vs >cT2N0 disease), renal function (CrCl ≥60 mL/min vs ≥40 to <60 mL/min), and PD-L1 status (high vs low/negative).

The dual primary endpoints were EFS and pathologic complete response, with OS as an alpha controlled secondary endpoint. Dr. Powles noted that after the data cut-off of January 2022, the pathologic complete response formal analysis was not statistically significant.

After a data cut-off of April 2024 and a median EFS follow-up of 42.3 months, the median EFS was significantly longer in the durvalumab arm versus the comparator arm (EFS hazard ratio, 0.68; 95% CI, 0.56-0.82; P<.000; OS hazard ratio, 0.75; 95% CI, 0.59-0.93; P=.0106).

RC was undergone in 88% and 83% of patients, respectively. After RC, 82% initiated adjuvant durvalumab.

Grade 3/4 treatment-related adverse events (TRAEs) occurred in 41% of patients in each arm, and TRAEs led to discontinuation of neoadjuvant treatment in 15% of patients. Dr. Powles noted that 8% of patients discontinued adjuvant durvalumab due to TRAEs.

Treatment-related deaths occurred in 0.6% of patients in each arm, he added.

“Perioperative durvalumab plus NAC demonstrated a statistically significant and clinically meaningful improvement in EFS and OS versus NAC alone and addition of neoadjuvant durvalumab did not compromise the ability to complete RC in patients with MIBC,” Dr. Powles concluded.