AstraZeneca's Imfinzi (durvalumab) has shown a clinically meaningful survival benefit in patients with muscle-invasive bladder cancer (MIBC) when administered in a perioperative regimen. The Phase III NIAGARA trial evaluated Imfinzi in combination with chemotherapy before cystectomy, followed by Imfinzi after surgery, compared to neoadjuvant chemotherapy followed by radical cystectomy. The results, presented at the 2024 European Society for Medical Oncology Congress (ESMO 2024), indicate a significant improvement in both event-free survival (EFS) and overall survival (OS).
NIAGARA Trial Results
The NIAGARA study demonstrated that the perioperative Imfinzi regimen led to a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death (p < 0.0001). At the time of analysis, the estimated EFS was not yet reached in the Imfinzi arm, compared to 46.1 months in the comparator arm. At two years, 67.8% of patients treated with Imfinzi were event-free, compared to 59.8% in the chemotherapy-only arm.
Furthermore, the Imfinzi regimen significantly improved overall survival, reducing the risk of death by 25% compared to radical cystectomy with neoadjuvant chemotherapy. This marks the first immunotherapy regimen to significantly extend overall survival in muscle-invasive bladder cancer.
Safety and Tolerability
The perioperative Imfinzi regimen was reported to be well-tolerated, with no new safety signals identified. The addition of Imfinzi to neoadjuvant chemotherapy did not impair patients' ability to complete surgery compared to neoadjuvant treatment alone.
Expert Commentary
Susan Galbraith, AstraZeneca’s executive vice president of Oncology R&D, highlighted the significance of the NIAGARA data, stating that perioperative Imfinzi can elicit “compelling improvements” in muscle-invasive bladder cancer. She emphasized that this regimen validates AstraZeneca's strategy to move cancer treatment as early as possible to maximize patient benefit.
Context of Perioperative Immunotherapy
These findings come at a time when the FDA is re-evaluating the risk/benefit profile of perioperative immunotherapy regimens in cancer treatment. A previous Imfinzi application for non-small cell lung cancer (NSCLC) prompted an Oncologic Drugs Advisory Committee meeting to assess the potential overtreatment of patients receiving PD-L1 therapy both before and after surgery. The committee raised concerns about exposing patients to excessive adverse events and emphasized the need for improved trial designs to delineate the therapeutic effect of each treatment phase.
