On March 28, 2025, the US Food and Drug Administration approved perioperative durvalumab plus neoadjuvant chemotherapy in resectable muscle-invasive bladder cancer based on data from the NIAGARA trial.
The cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, and Rohit Gosain, MD, spoke with the trial’s lead author, Thomas Powles, MD, MBBS, MRCP, of Barts Cancer Institute, to discuss key findings from the study.
NIAGARA Trial Design
The NIAGARA trial evaluated combining durvalumab with 4 cycles of neoadjuvant gemcitabine-cisplatin chemotherapy prior to radical cystectomy, then administering 8 cycles of durvalumab after surgery.
The dual primary endpoints were event-free survival (EFS) and pathological complete response (pCR), with OS as a key secondary endpoint. The trial enrolled patients with tumor stages ranging from T2 to T4a and also included a small proportion with N1-positive disease, according to Dr. Powles.
Dr. Rahul Gosain asked whether a third treatment arm could have been included to evaluate durvalumab in only the neoadjuvant regimen, noting that the benefit of postoperative immunotherapy is unclear.
Dr. Powles responded that NIAGARA—despite being one of the largest neoadjuvant therapy bladder cancer trials to date—would have needed far more patients to include a third treatment arm while remaining powered for the survival endpoints. “[NIAGARA] doesn’t answer all of the questions, but what it does tell us is early immune checkpoint inhibition saves lives and is associated with a significant survival advantage,” he said.
Perioperative Durvalumab in NIAGARA
The NIAGARA data showed that perioperative durvalumab yielded a significant benefit to both EFS and OS. Additionally, the survival benefit was consistent across broad subgroups including tumor staging, disease location, split dosing of cisplatin, and geographical area.
At 24 months, the OS rate was 82.2% in the durvalumab arm compared with 75.2% in the standard of care arm. Overall, the durvalumab arm had a 25% reduced risk of death (hazard ratio, 0.75; 95% CI, 0.59-0.93).
Additionally, in follow-up analyses, the 26-month EFS rates in the durvalumab and standard of care arms were 92.1% versus 85.8% for patients with pCR and 53.3% versus 49.5% for patients without pCR.
Importantly, more patients in the durvalumab arm went on to receive surgery without an increase in delays, surgical toxicity, adverse events, or postoperative complications compared with the control arm. Altogether, Dr. Powles summarized, perioperative durvalumab improved OS with no detrimental impact on surgical outcomes.
Treating Beyond Durvalumab
Winding down the discussion, the doctors briefly considered treatment options for patients who progress or relapse after durvalumab, while noting that rechallenging with immunotherapy has not been effective in several clinical trials.
Patients like those in NIAGARA who have been exposed to platinum-based chemotherapy and immunotherapy have very few attractive options, Dr. Powles stated.
Based on the current data, he considers enfortumab vedotin with or without pembrolizumab to be the right choice; however, if enfortumab vedotin plus pembrolizumab is implemented in the neoadjuvant setting, follow-up treatment options are again uncertain.
