Additional NIAGARA data spotlight benefits of durvalumab plus chemo for MIBC

Additional data from the phase 3 NIAGARA trial (NCT03732677) bolster the safety and efficacy of perioperative durvalumab (Imfinzi) plus neoadjuvant chemotherapy followed by radical cystectomy and adjuvant chemotherapyin patients with cisplatin-eligible muscle-invasive bladder cancer.¹

Matthew Galsky, MD

“For decades, there’s been no improvement in clinical outcomes for patients with muscle-invasive bladder cancer beyond what could be achieved by neoadjuvant chemotherapy followed by cystectomy. The tide is finally starting to turn with the introduction of immune checkpoint blockade to the muscle-invasive bladder cancer setting,” study investigator Matthew Galsky, MD, said during his presentation at the 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco, California. Galsky is a professor of medicine (Hematology and Medical Oncology), director of Genitourinary Medical Oncology, co-director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute, and associate director for Translational Research at The Tisch Cancer Institute in New York, New York.

Previously reported and published results from NIAGARA found that regarding event-free survival (EFS), there was a significant reduction in risk (HR=0.68, 95% CI, 0.56-0.82). Median follow-up was 42.3 months (range, 0.03-61.3 months).^2,3

“At 2 years, the landmark EFS is 68% vs 60%, an 8% delta,” said Thomas B. Powles, MBBS, MRCP, MD, during his presentation at the 2024 European Society for Medical Oncology Congress in Barcelona, Spain.

“The overall survival [OS] showed a 25% reduction in the risk of death. This is statistically significant,” Powles said. There were 136 deaths (25.5%) in the durvalumab arm vs 169 deaths (31.9%) in the comparator arm (HR=0.75, 95% CI, 0.59-0.93, P = .0106).

At ASCO GU, Galsky presented additional safety and efficacy data from NIAGARA. The patient population consisted of adults with cisplatin-eligible MIBC (cT2-T4aN0/1M0), urothelial cancer or urothelial cancer with divergent differentiation or histologic subtypes, evaluated and confirmed for radical cystectomy, and with creatine clearance of 40 mL/min or lower. Patient were randomly assigned 1:1 to either the durvalumab arm or the comparator arm. Patients in the durvalumab arm received neoadjuvant durvalumab, 1500 mg intravenously Q3W and gemcitabine plus cisplatin for 4 cycles followed by radical cystectomy and 8 cycles of adjuvant durvalumab. Patients in the comparator arm received 4 cycles of gemcitabine plus cisplatin for 4 cycles followed by radical cystectomy. The 2 primary end points were EFS and pathological complete response. A key secondary end point was OS. Other secondary end points included metastasis-free survival, disease-specific survival, and safety. In the exploratory post hoc analysis, the investigators evaluated both EFS and OS by pathological complete response (pCR).

“Consistent with the primary end point analysis, the addition of perioperative durvalumab to neoadjuvant chemotherapy improved metastasis-free survival, with a hazard ratio of 0.67. The 24-month metastasis-free survival rate was increased by 10% in the durvalumab arm compared to the comparator arm. Similarly, disease-specific survival was improved, with a hazard ratio of 0.69 favoring the durvalumab arm,” Galsky reported.

The pCR was 37.3% (95% CI, 33.2-41.6) in the durvalumab arm and 27.5% (95% CI, 23.8-31.6) in the comparator arm. The investigators also assessed baseline patient characteristics in patients achieving and not achieving a pCR, and Galsky reported that they found “no major differences” in characteristics between the treatment and comparator arms.

“Patients achieving a pathological complete response overall had longer event-free survival compared to patients not achieving a pathological complete response. However, the addition of perioperative durvalumab to neoadjuvant chemotherapy was associated with an improvement in event-free survival both in patients achieving a pathological complete response, with a hazard ratio of 0.58, and in patients not achieving a pathological complete response, with a hazard ratio of 0.77,” Galsky said.

Patients achieving a pCR had longer OS than patients who did not achieve a pCR. “However, there was a trend toward improved overall survival with perioperative durvalumab both in patients achieving a pathological complete response and those not achieving a pathological complete response,” Galsky said.

Regarding safety, adverse events (AEs) of any cause occurred in 527 (99%) patients in the durvalumab arm vs 525 (100%) of patients in the comparator arm. Grade 3-4 AEs were observed in 368 (69%) patients in the durvalumab arm vs 355 (68%) patients in the comparator arm. Fifty (9%) patients experienced AEs leading to discontinuation of durvalumab, and 72 (14%) experienced AEs leading to discontinuation of neoadjuvant chemotherapy in the durvalumab arm vs 80 (15%) in the comparator arm. Six (1%) patients had AEs leading to them not undergoing radical cystectomy in the durvalumab arm vs 7 (1%) patients in the comparator arm. Nine (2%) patients had AEs leading to a delay in surgery in the durvalumab arm vs 6 (1%) patients in the comparator arm. Incidence of grade 3-4 AEs was 41% in both treatment arms.

Immune-mediated AEs occurred in 21% of patients in the durvalumab arm. These were mostly grade 1-2, “and consistent with the known profile of durvalumab,” Galsky said. The most common immune-related AEs were hypothyroid events, which occurred in 10% of patients in the durvalumab arm.

“As previously reported, NIAGARA…demonstrated a statistically significant and clinically meaningful improvement in event-free survival, with a hazard ratio of 0.68, and overall survival, with a hazard ratio of 0.75, along with a 10% increase in pathological complete response rate…On exploratory analysis, the benefits of perioperative durvalumab were conferred in both patients achieving a path[ological] CR and in patients not achieving a path[ological] CR…These additional data further support perioperative durvalumab with neoadjuvant chemotherapy as a potential new treatment for cisplatin-eligible patients with muscle-invasive bladder cancer,” Galsky said in his concluding remarks.

REFERENCES

1. Galsky M, Van Der Heijden M, Catto J, et al. Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA. J Clin Oncol 43, 2025 (suppl 5; abstr 659). doi:10.1200/JCO.2025.43.5_suppl.659

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. https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/session/calendar?q=LBA5

3. Powles T, Catto JWF, Galsky MD, et al. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer. N Engl J Med. 2024 Nov 14;391(19):1773-1786. doi:10.1056/NEJMoa2408154