FDA Approval and Trial Background

On March 28, 2025, the FDA approved a significant advancement in treating muscle-invasive bladder cancer (MIBC) in adults. The approval establishes a treatment protocol that begins with neoadjuvant therapy combining AstraZeneca's durvalumab (brand name: Imfinzi) with gemcitabine and cisplatin before surgery. Following radical cystectomy, the treatment continues with adjuvant therapy using durvalumab alone.

Study Design

This open-label, randomized, and multicenter Phase 3 clinical trial—NIAGARA (NCT03732677)—enrolled 1063 patients. These patients were candidates for radical cystectomy with no prior systemic therapy for bladder cancer. Patients were randomized (1:1) to receive either neoadjuvant durvalumab with chemotherapy followed by adjuvant durvalumab after surgery or neoadjuvant chemotherapy followed by surgery alone.

Efficacy and Safety

The main efficacy outcome is event-free survival (EFS) measured by blinded independent central review. Overall survival (OS) was also measured. At a pre-determined interim evaluation, the study showed a statistically significant improvement in both EFS and OS. The median EFS was not reached (NR) in the durvalumab+ chemotherapy arm. Similarly, the median OS was not reached in either arm.

Median EFS:

Durvalumab + chemo: NR (95% CI: NR, NR) Chemo alone: 46.1 months (95% CI: 32.2, NR) Hazard ratio: 0.68 (95% CI: 0.56, 0.82) Two-sided p-value: <0.0001

Median OS:

Both arms: NR Hazard ratio: 0.75 (95% CI: 0.59, 0.93) Two-sided p-value: 0.0106

Regarding safety, the adverse reactions were consistent with known prior experience with durvalumba with platinum-based chemotherapy.

For patients weighing 30 kg or more, the recommended durvalumab dose is 1,500 mg every 3 weeks with chemotherapy (neoadjuvant) and 1,500 mg every 4 weeks as a single agent (adjuvant). For those weighing less than 30 kg, the dose is 20 mg/kg every 3 weeks with chemotherapy and 20 mg/kg every 4 weeks as a single agent. The FDA recommends that treatment continue until the disease progresses and prevents surgery, the cancer returns, side effects become too severe, or a maximum of 8 cycles are completed after surgery.

About Durvalumab

Durvalumab is a monoclonal antibody used to treat cancers affecting the urinary tract and lungs. It works as a programmed death-ligand 1 (PD-L1) inhibitor to mount immune responses that attack tumor cells. It has been indicated for Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC), Biliary tract cancer, Hepatocellular carcinoma, and Endometrial cancer.

About Cisplatin

Cisplatin is a platinum-based chemotherapy drug used to treat various cancers, including sarcomas, carcinomas, lymphomas, and germ cell tumors. It belongs to the alkylating agent class of chemotherapy drugs and works by causing cross-linking in the DNA double helix. This disrupts the cell division process, ultimately leading to tumor cell death.

About Gemcitabine

Gemcitabine is a chemotherapy drug used to treat advanced stages of various cancers, including ovarian, breast, pancreatic, and certain types of lung cancer. Marketed as Gemzar, gemcitabine is a nucleoside analog that works by replacing the building blocks of DNA, which disrupts DNA elongation, causing tumor cell death.

About Muscle-Invasive Bladder Cancer (MIBC)

MIBC is a form of bladder cancer that grows into the muscle layer of the bladder wall. This type of cancer is highly metastatic and tends to be harder to treat, with a high risk of recurrence. New treatment options, such as immune checkpoint inhibitors and targeted therapies (including antibody-drug conjugates and FGFR inhibitors), have shown benefits in advanced disease. Currently, several clinical trials are investigating the promising role of these therapies, either as single agents or in combination with chemotherapy.

For further information, please refer to the clinical trial details and the FDA official announcement.