FDA Grants Priority Review to Durvalumab for Muscle-Invasive Bladder Cancer

Sebastian Kaulitzki – stock.adobe.com

The FDA has granted priority review to the supplemental biologics license application (sBLA) seeking the approval of durvalumab (Imfinzi) for the treatment of patients with muscle-invasive bladder cancer (MIBC).¹

The sBLA is supported by data from the phase 3 NIAGARA trial (NCT03732677). Findings presented at the 2024 ESMO Congress demonstrated that at a median follow-up of 42.3 months (range, 0.03-61.3), patients treated with neoadjuvant durvalumab plus gemcitabine and cisplatin, followed by adjuvant durvalumab (n = 533) experienced a median event-free survival (EFS) that was not reached (NR; 95% CI, NR-NR) compared with 46.1 months (95% CI, 32.2-NR) for those given neoadjuvant gemcitabine plus cisplatin, followed by no adjuvant treatment (n = 530; HR, 0.68; 95% CI, 0.56-0.82; stratified log-rank P < .0001).² The 12- and 24-month EFS rates in the durvalumab arm were 76.0% and 67.8%, respectively. These respective rates were 69.9% and 59.8% in the control arm.

A re-analysis of pathologic complete response (pCR) rates showed that patients in the durvalumab arm achieved a pCR rate of 37.3% (95% CI, 33.2%-41.6%) compared with 27.5% (95% CI, 23.8%-31.6%) in the control arm (OR, 1.60; 95% CI, 1.23-2.08; P = .0005).

“New options for MIBC are vital because nearly half of patients will see their cancer return or progress despite undergoing curative-intent treatment, including removal of their bladder,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, stated in a news release.¹ “Today’s priority review designation recognizes the urgent need for new options for these patients and the potential of [durvalumab] to transform the standard of care as the first and only perioperative immunotherapy regimen to delay recurrence and extend survival in this setting.”

The global NIAGARA trial enrolled adult patients with cisplatin-eligible MIBC (cT2-T4aN0/1M0).² Patients could have urothelial carcinoma or urothelial carcinoma with divergent differentiation or histologic subtypes, and they needed to be evaluated and confirmed for radical cystectomy. A creatine clearance of at least 40 mL per minute was also required.

Patients were randomly assigned 1:1 to receive neoadjuvant durvalumab at 1500 mg once every 3 weeks plus gemcitabine and cisplatin for 4 cycles, followed by radical cystectomy and adjuvant durvalumab at 1500 mg once every 4 weeks for 8 cycles; or neoadjuvant gemcitabine plus cisplatin for 4 cycles, followed by radical cystectomy and no adjuvant treatment.

Stratification factors included clinical tumor stage (T2N0 vs > T2N0), renal function (creatinine clearance of ≥ 60 mL/min vs ≥ 40 to < 60 mL/min), and PD-L1 status (high vs low/negative expression).

EFS and pCR rates served as the trial’s dual primary end points. Secondary end points included overall survival (OS), disease-free survival, disease-specific survival, metastasis-free survival, health-related quality of life, and 5-year OS.

Additional data showed that an OS trend was observed favoring the durvalumab arm (HR, 0.75; 95% CI, 0.59-0.93; stratified log-rank P = .0106). The 12- and 24-month OS rates in the experimental arm were 89.5% and 82.2%, respectively. These respective rates were 86.5% and 75.2% in the control arm.

Regarding safety, any-grade adverse effects (AEs) were reported in 99% of patients in the durvalumab arm (n = 530) and all patients in the control arm (n = 526). The rates of grade 3/4 AEs were 69% and 68%, respectively, and the respective rates of serious AEs were 62% and 55%. AEs led to death in 5% of patients in the durvalumab arm vs 6% of patients in the control arm. In the experimental arm, AEs led to discontinuation of study treatment in 21% of patients and discontinuation of neoadjuvant durvalumab in 9% of patients. Fifteen percent of patients in the control arm discontinued study treatment due to AEs.

Any-grade AEs possibly related to treatment occurred in 95% of patients in the durvalumab arm vs 93% of patients in the control arm. The rates of grade 3/4 AEs possibly related to study treatment were 41% in both arms. Possible treatment-related AEs led to death in 0.6% of patients in both arms. The rates of any-grade immune-mediated AEs were 21% in the experimental arm vs 3% in the control arm.

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). Ann Oncol. 2024;35(suppl 2):S1271. doi:10.1016/j.annonc.2024.08.2327