Additional NIAGARA data reinforce benefit of perioperative durvalumab in MIBC

The addition of durvalumab (Imfinzi) to neoadjuvant chemotherapy did not affect the rate or timing of radical cystectomy and did not lead to an increased rate of surgical complications in patients with cisplatin-eligible muscle-invasive bladder cancer (MIBC), according to additional data from the phase 3 NIAGARA trial (NCT03732677).¹

James W.F. Catto, MBChB, PhD, FRCS

The data were presented by James W.F. Catto, MBChB, PhD, FRCS, at the 40th Annual European Association of Urology (EAU) Congress in Madrid, Spain.

Initial data from the NIAGARA trial were shared at the 2024 European Society for Medical Oncology Congress in Barcelona, Spain and published in The New England Journal of Medicine.^2,3 Overall, data showed that the addition of durvalumab to neoadjuvant chemotherapy prior to radical cystectomy significantly improved overall survival (24-month OS, 82.2% vs 75.2%; P = .0106) and event-free survival (24-month EFS, 67.8% vs 59.8%; P < .0001) compared with neoadjuvant chemotherapy alone. The combination also led to a 10% improvement in pathological complete response rate (37.3% vs 27.5%; P = .0005).

In the presentation at the EAU Congress, Catto began by stating, “It's an honor to be here talking about NIAGARA, which is the first prospective randomized trial to show an overall survival benefit in muscle invasive bladder cancer with neoadjuvant treatment. We can't underestimate the importance of that.”

The current analyses focused on the impact that adding durvalumab had on surgical outcomes, as well as neoadjuvant safety data with the combination.

Overall, the addition of durvalumab did not appear to affect the rate of surgical completion. In the durvalumab plus chemotherapy arm, 469 patients (88%) underwent radical cystectomy compared with 441 patients (83%) in the chemotherapy alone arm.

Tumor characteristics were well balanced between both arms. In total, 60% of patients in both arms had higher than T2N0 disease.

Catto added, “[Overall,] 60% of people and 70% of people had a hysterectomy and an oophorectomy, but the new EAU guidelines are much more about organ-preserving approaches in women, so perhaps we'll see a pullback toward more organ preservation.”

The median time from the last dose of neoadjuvant chemotherapy to radical cystectomy was 5.6 weeks (range, 1.1-16.9 weeks) in the combination arm vs 5.4 weeks (range, 1.7-47.6 weeks) in the chemotherapy arm. In the durvalumab arm, 90% and 96% of patients had cystectomy within 56 days and 70 days following the last dose of neoadjuvant chemotherapy, respectively. In the chemotherapy alone arm, 90% and 95% of patients had undergone cystectomy within 56 and 70 days following the last dose of chemotherapy, respectively.

The proportion of patients with surgical complications was also comparable between both study arms. Approximately 16% of patients in each arm experienced a complication of grade 3 or higher.

Similarly, 93% of patients in each arm experienced a treatment-related adverse event (TRAE) during the neoadjuvant study period. TRAEs of grades 3 or 4 were reported in 38% of patients in the combination arm vs 41% of patients in the comparator arm.

The most common (10% or higher) AEs during the neoadjuvant study period included nausea (51% durvalumab/chemotherapy vs 46% chemotherapy), neutropenia (40% vs 45%), and fatigue (33% vs 30%).

Catto noted, “Neutropenia was the most concerning issue, but that's being driven by the chemotherapy.”

Additionally, immune-mediated AEs in the combination arm were generally low grade and consistent with previously reported safety data on durvalumab.These AEs were primarily driven by hypothyroid (3%) and hyperthyroid (2%) events. The median time to onset was 73 days (range, 29-141) for the hypothyroid events and 38 days (range, 22-112) for the hyperthyroid events.

In total, the NIAGARA trial enrolled 1063 patients with cisplatin-eligible MIBC. Patients were randomly assigned 1:1 to receive durvalumab plus chemotherapy (n = 533) or to chemotherapy alone (n = 530) followed by radical cystectomy. In the combination arm, patients also received 8 cycles of adjuvant durvalumab.

The primary end points for the study were event-free survival and pathological complete response. Overall survival was a key secondary end point. Safety end points include immune-mediated AEs.

Overall, Catto concluded during the presentation, “The addition of the durvalumab did not make treatment more morbid than chemotherapy alone, and it didn't change or increase the surgical complications you saw in the ward. It gives us a very safe signal for that approach for our patients. The immune mediated adverse events aren’t new. They're rare, and apart from thyroid function, they're mostly happening before they come to a urologist. I think we can feel reassured by that.”

REFERENCES

1. Catto JWF, Al-Ahmadie H, van der Heijden MS, et al. Surgical outcomes and neoadjuvant safety with perioperative durvalumab for muscle-invasive bladder cancer (NIAGARA). Presented at: 40^th Annual European Association of Urology Congress. Madrid, Spain. March 21-24, 2025. Abstract GC2

2. Powles TB, van der Heijden MS, Galsky MD, et al. A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA). Presented at: 2024 European Society for Medical Oncology Annual Congress. September 13-17, 2024. Barcelona, Spain. Abstract LBA5

3. Powles T, Catto JWF, Galsky MD. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer. N Engl J Med. Published online September 15, 2024. Accessed March 24, 2025. https://www.nejm.org/doi/abs/10.1056/NEJMoa2408154