Positive results from the phase III NIAGARA trial showed perioperative treatment with the PD-L1 blocker durvalumab in combination with neoadjuvant chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival and the key secondary endpoint of overall survival vs neoadjuvant chemotherapy alone for patients with muscle-invasive bladder cancer. Patients were treated with durvalumab in combination with neoadjuvant chemotherapy before radical cystectomy followed by durvalumab as adjuvant monotherapy.
These results were presented during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2024 (Abstract LBA5) and simultaneously published in The New England Journal of Medicine.
Key Findings
In a planned interim analysis, patients treated with the durvalumab perioperative regimen showed a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death vs the comparator arm (based on an event-free survival hazard ratio [HR] of 0.68; 95% confidence interval [CI] = 0.56–0.82; P < .0001). Estimated median event-free survival was not yet reached for the durvalumab arm vs 46.1 months for the comparator arm. An estimated 67.8% of patients treated with the durvalumab regimen were event-free at 2 years compared to 59.8% in the comparator arm.
Results from the key secondary endpoint of overall survival showed the durvalumab perioperative regimen reduced the risk of death by 25% vs neoadjuvant chemotherapy with radical cystectomy (HR = 0.75; 95% CI = 0.59–0.93; P = .0106). Median survival was not yet reached for either arm. An estimated 82.2% of patients treated with the durvalumab regimen were alive at 2 years vs 75.2% in the comparator arm.
Durvalumab was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding durvalumab to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery compared to neoadjuvant chemotherapy alone. Grade 3 or 4 adverse events due to any cause occurred in 69% of patients treated with durvalumab and 68% of patients treated with neoadjuvant chemotherapy.
Results in Perspective
Thomas Powles, MD, PhD
Thomas Powles, MD, PhD, Director of Barts Cancer Centre, London, and principal investigator in the NIAGARA trial, said: “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. Adding durvalumab 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.”
In addition to NIAGARA, durvalumab is being tested across early- and late-stage bladder cancer in various treatment combinations, including in non–muscle-invasive disease (POTOMAC), patients with muscle-invasive bladder cancer who are cisplatin-ineligible or refusing cisplatin (VOLGA), and locally advanced or metastatic disease (NILE).
Disclosure: Dr. Powles reported financial relationships with AstraZeneca, Bristol Myers Squibb, Exelixis, Gilead, Incyte, Ipsen, Mashup Ltd, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, and MSD. For full disclosures of the study authors, visit cslide.ctimeetingtech.com/esmo2024/attendee/confcal/session.
