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Findings from the Phase III NIAGARA trial (NCT03732677) show that Imfinzi (durvalumab) in combination with chemotherapy significantly improved event-free survival (EFS) and overall survival (OS) compared to neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC).1-3 Results from the study, published by The New England Journal of Medicine, show Imfinzi is the first immunotherapy regimen to produce statistically significant and clinically meaningful OS improvements before and following surgery, according to the trial investigators.1
“Neoadjuvant chemotherapy with bladder removal has been the mainstay of treatment for patients with muscle-invasive bladder cancer for nearly 20 years; however, half of patients still go on to suffer a devastating recurrence,” principal NIAGARA investigator Thomas Powles, MD, director of Barts Cancer Centre, London, UK, said in a press release. “Adding [Imfinzi] before and after surgery significantly reduced the chance of recurrence and extended survival, a significant advance with the potential to transform the standard of care for these patients who desperately need better outcomes.”1
The study authors noted that standard therapy for cisplatin-eligible patients with MIBC involves neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy with pelvic-lymph-node dissection, but 50% of patients with MIBC experience disease recurrence within three years.
Imfinzi, a selective, high-affinity human IgG1 monoclonal antibody, attaches to PD-L1 and blocks interactions with PD-1 and CD80 on activated T cells. Current FDA-approved indications for Imfinzi include for the treatment of unresectable, stage III non-small cell lung cancer (NSCLC) in patients with disease that has not progressed following chemoradiation therapy; for the treatment of extensive-stage small-cell lung cancer; combined with a limited course of Imjudo (tremelimumab) and chemotherapy to treat metastatic NSCLC; in combination with gemcitabine plus cisplatin to treat locally advanced or metastatic biliary tract cancer; and in combination with Imjudo to treat unresectable hepatocellular carcinoma. Additionally, the drug was approved last month in combination with chemotherapy for adult patients with resectable early-stage (IIA-IIIB) NSCLC without EGFR mutations or ALK rearrangements.
The randomized, open-label, multi-center, global NIAGARA trial analyzed treatment with Imfinzi before and following radical cystectomy in patients with MIBC. Investigators randomly assigned 1,063 patients to receive Imfinzi plus chemotherapy or chemotherapy alone prior to cystectomy, followed by Imfinzi or no further treatment post-surgery. The trial’s dual primary endpoints are EFS, defined as the time from randomization to the occurrence of an event such as tumor recurrence or progression and pathologic complete response, with key secondary endpoints of OS and safety.
A total of 533 patients were randomly assigned to the Imfinzi cohort and 530 to the comparison cohort. Patients administered the Imfinzi perioperative regimen achieved a 32% decrease in the risk of disease progression, recurrence, not undergoing surgery, or death compared with the comparison cohort (based on EFS hazard ratio [HR] of 0.68; 95% confidence interval [CI] 0.56-0.82; p<0.0001). Estimated median EFS was not yet reached in the Imfinzi cohort compared to 46.1 months in the comparison cohort.
Estimated EFS at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the Imfinzi cohort compared to 59.8% (95% CI, 55.4 to 64.0) in the comparison cohort (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). Estimated OS at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the Imfinzi cohort compared to 75.2% (95% CI, 71.3 to 78.8) in the comparison cohort (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P=0.01 by stratified log-rank test).
“The NIAGARA data showed compelling improvements in both [EFS] and [OS], with more than 80% of patients treated with the Imfinzi perioperative regimen alive at two years,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in a press release. “This is the first immunotherapy regimen to significantly extend [OS] in [MIBC], and it further validates our strategy to move cancer treatment as early as possible to maximize benefit for patients.”1
In terms of safety, grade 3 or 4 treatment-related adverse events (TRAEs) were reported by 40.6% of the patients in the Imfinzi cohort compared to in 40.9% of patients in the comparison cohort. TRAEs causing death occurred in 0.6% in each cohort. Approximately 88% of patients in the Imfinzi cohort underwent radical cystectomy compared to 83.2% of patients in the comparison cohort.
“Perioperative [Imfinzi] with neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy provided a significant [EFS] benefit and [OS] benefit to patients with [MIBC],” the study authors concluded. “The results of this trial support the use of perioperative [Imfinzi] with neoadjuvant chemotherapy as a potential new treatment option for cisplatin-eligible patients with [MIBC].”3
References
1. Imfinzi perioperative regimen reduced the risk of recurrence by 32% and the risk of death by 25% vs. neoadjuvant chemotherapy alone in muscle-invasive bladder cancer in the NIAGARA Phase III trial. News release. AstraZeneca. September 15, 2024. Accessed September 19, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-perioperative-regimen-reduced-risk-recurrence-by-32-risk-death-by-25-vs-neoadjuvant-chemotherapy-alone-in-mibc-niagara-phase-iii-trial.html
2. Durvalumab+ Gemcitabine/Cisplatin (Neoadjuvant Treatment) and Durvalumab (Adjuvant Treatment) in Patients With MIBC (NIAGARA). ClinicalTrials.gov. Updated July 1, 2024. Accessed September 19, 2024. https://clinicaltrials.gov/study/NCT03732677
3. Powles T., et al. Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer. N Engl J Med. Online. Published September 15, 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2408154