FDA grants priority review to durvalumab for muscle-invasive bladder cancer

The FDA has granted a priority review designation to a supplemental Biologics License Application (sBLA) for durvalumab (Imfinzi) in patients with muscle-invasive bladder cancer (MIBC), AstraZeneca announced in a news release.¹

“The overall survival showed a 25% reduction in the risk of death. This is statistically significant,” said Thomas B. Powles, MBBS, MRCP, MD.

According to the company, “The FDA action date for their regulatory decision is anticipated in the second quarter of 2025.”

The priority review decision is based on results of the phase 3 NIAGARA study (NCT03732677), presented at the 2024 European Society for Medical Oncology Congress in Barcelona, Spain and published in The New England Journal of Medicine.^2,3

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 event-free survival (EFS) and pathological complete response (pCR).

A total of 1530 patients were enrolled and 1063 patients were randomly assigned, with 533 patients assigned to the durvalumab arm and 530 assigned to the comparator arm.

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).

“At 2 years, the landmark EFS is 68% vs 60%, an 8% delta,” said study investigator Thomas B. Powles, MBBS, MRCP, MD, director of the Barts Cancer Centre at St. Bartholomew’s Hospital in London, United Kingdom.

The investigators also conducted an EFS sensitivity analysis in which patients who did not undergo radical cystectomy were censored. In this analysis, the HR was 0.69 (95% CI, 0.56-0.86), which Powles said was “reassuring.”

“The overall survival 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).

Powles reported that adverse events (AEs) “were balanced in both arms.” Grade 3 or 4 AEs occurred in 368 (69%) patients in the durvalumab arm vs 355 (68%) patients in the comparator arm. The rate of grade 3 or 4 treatment-related AEs was 41% in both arms. AEs leading to discontinuation of neoadjuvant chemotherapy occurred in 72 (14%) patients in the durvalumab arm vs 80 (15%) patients in the comparator arm.

“New options for muscle-invasive bladder cancer are vital because nearly half of patients will see their cancer return or progress despite undergoing curative-intent treatment, including removal of their bladder,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in the news release.² “Today’s Priority Review designation recognizes the urgent need for new options for these patients and the potential of IMFINZI to transform the standard of care as the first and only perioperative immunotherapy regimen to delay recurrence and extend survival in this setting.”

REFERENCES

1. IMFINZI (durvalumab) granted Priority Review in the US for patients with muscle-invasive bladder cancer. News release. AstraZeneca. December 6, 2024. Accessed December 6, 2024. https://www.astrazeneca-us.com/media/press-releases/2024/imfinzi-durvalumab-granted-priority-review-in-the-us-for-patients-with-muscle-invasive-bladder-cancer.html

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. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer. N Engl J Med. 2024;391:1773-1786. doi:10.1056/NEJMoa2408154