FDA Grants Priority Review to Durvalumab/Chemo in Bladder Cancer

The FDA set a Prescription Drug User Fee act date in the second quarter of 2025 for durvalumab plus chemotherapy in muscle-invasive bladder cancer.

A supplemental biologics license application (sBLA) for durvalumab (Imfinzi) plus chemotherapy, as a treatment for patients with muscle-invasive bladder cancer (MIBC), has been granted priority review in the US by the FDA, according to a press release from the developer, AstraZeneca.1

A Prescription Drug User Fee Act date is anticipated during the second quarter of 2025. Additionally, based on relevant trial results, regulatory applications for durvalumab are under review worldwide in the EU, Japan, and several other countries.

The decision is based on results from the open-label, randomized phase 3 NIAGARA trial (NCT03732677) presented at the 2024 European Society for Medical Oncology Congress.2 The trial evaluated a treatment of neoadjuvant durvalumab plus gemcitabine/cisplatin followed by radical cystectomy then durvalumab as a monotherapy compared with neoadjuvant gemcitabine/cisplatin alone followed by radical cystectomy in cisplatin-eligible patients with MIBC.

“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 Research and Development at AstraZeneca, said in a press 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.”

Perioperative durvalumab plus chemotherapy showed a 32% drop in the risk of disease progression, recurrence, not undergoing surgery, or death when compared with neoadjuvant chemotherapy with radical cystectomy alone (event-free survival [EFS] HR, 0.68; 95% CI, 0.56-0.82; P <.0001). At 2 years, it was estimated that 67.8% of patients treated with durvalumab were event free compared with 59.8% of patients in the control arm.

A key secondary end point was overall survival (OS); the durvalumab regimen reduced the risk of death by 25% compared with the neoadjuvant chemotherapy alone regimen (HR, 0.75; 95% CI, 0.59-0.93; P = .0106). At 2 years, an estimated 82.2% of patients given the durvalumab regimen were alive compared with 75.2% of patients given the chemotherapy alone. For both arms, median OS was not reached.

Patients were assigned, in a 1:1 ratio, and stratified by clinical tumor stage, renal function, and tumor PD-L1 expression level, to either the durvalumab group (n = 533) or the control group (n = 530).3 Patients in the experimental group received 1500 mg of neoadjuvant durvalumab for 4 cycles along with 1000 mg/m2 of gemcitabine and 70 mg/m2 of cisplatin given on day 1, followed by 1000 mg/m2 of gemcitabine on day 8 administered intravenously every 3 weeks followed by radical cystectomy and then up to 8 cycles of 1500 mg of adjuvant durvalumab given every 4 weeks. The control group was administered the same gemcitabine/cisplatin dosage followed by radical cystectomy.

To be eligible, patients had to be 18 years or older with histologically or cytologically documented MIBC with a tumor stage of T2, T3, or T4a, N0 or N1, and M0. They had to be eligible for cisplatin-based chemotherapy and be medically fit to complete radical cystectomy.

Previous systemic chemotherapy or immunotherapy for MIBC, pure nonurothelial carcinoma, or small-cell histologic features were all notable exclusion criteria.

Regarding safety, 99.4% of patients in the durvalumab group and 99.8% of patients in the control group experienced at least one adverse event (AE) of any cause. Treatment-related AEs (TRAEs) were observed in 94.7% of patients in the durvalumab group and 92.6% of patents in the control group; TRAEs of grades 3 or 4 were observed in 40.6% and 40.9%, respectively.

AEs leading to discontinuation of neoadjuvant treatment occurred in 14.9% of patients in the durvalumab group and 15.2% of patients in the control group.

A total of 3 patients (0.6%) in each group experienced TRAEs leading to death. In the durvalumab group, all 3 were during neoadjuvant therapy; 1 to cardiorespiratory arrest, 1 to pulmonary embolism, and 1 to myocardial infarction. In the control group, 2 deaths were during neoadjuvant treatment, and 1 was after surgery.

References

1. Imfinzi granted Priority Review in the US for patients with muscle-invasive bladder cancer. News release. AstraZeneca. December 6, 2024. Accessed December 6, 2024. https://tinyurl.com/3cj6yvup
2. Powles T, Van der Heijden MS, Galsky M, 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 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA5.
3. Powles T, Catto JWF, Galsky MD, et al. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer. N Engl J Med. 2024;391(19):1773-1786. doi:10.1056/NEJMoa2408154