FDA Approves Durvalumab Combo for Muscle-Invasive Bladder Cancer

Durvalumab with gemcitabine and cisplatin plus adjuvant durvalumab is the only FDA-approved perioperative immunotherapy for muscle-invasive bladder cancer.

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Neoadjuvant durvalumab (Imfinzi; AstraZeneca) with gemcitabine and cisplatin plus adjuvant durvalumab has been approved as perioperative immunotherapy against muscle-invasive bladder cancer (MIBC), based on NIAGARA (NCT03732677) trial data.^1,2

This is the only FDA-approved perioperative immunotherapy for MIBC.

NIAGARA is an ongoing phase 3, randomized, open-label, multicenter, global study—the primary completion date is June 30, 2025, and the estimated completion date is June 30, 2026—with 2 arms. The experimental arm is receiving durvalumab, an anti–PD-L1 antibody, plus chemotherapy (cisplatin and gemcitabine), and the control arm is receiving the chemotherapy combination alone.³

To be included in NIAGARA, patients need to be treatment naive for systemic chemotherapy or immunotherapy to treat their resectable MIBC (clinical stage T2-T4aN0/1M0, transitional and mixed transitional cell histology), planning radical cystectomy, have an Eastern Cooperative Oncology Group performance status of 0 or 1, and a life expectancy of 12 weeks or more at randomization.

“This approval for the durvalumab-based perioperative regimen is a major breakthrough for people with muscle-invasive bladder cancer, nearly half of whom see their cancer return despite chemotherapy and surgery with curative-intent,” Matthew Galsky, MD, director of genitourinary medical oncology, The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, and NIAGARA investigator, said in a statement. “This durvalumab regimen significantly extended patients’ lives in the NIAGARA trial and has the potential to transform care.”

The perioperative regimen previously received a priority review from the FDA in December 2024, based on NIAGARA results showing statistically significant and clinically meaningful event-free (EFS) and overall survival (OS) benefits.⁴

What the Data Show¹

In the NIAGARA trial, patients in the treatment arm received 4 cycles of durvalumab plus neoadjuvant chemotherapy prior to radical cystectomy and 8 cycles of durvalumab monotherapy after radical cystectomy or neoadjuvant chemotherapy before radical cystectomy.

These most recent data, the product of an interim analysis, demonstrate overall positive outcomes upon comparing the former investigative combination and the control group, respectively:

• 32% reduced risk of disease progression, recurrence, not undergoing surgery, or death (HR, 0.68; 95% CI, 0.56-0.82; P < .0001)
• EFS that was not reached vs 46.1 months
• 67.8% vs 59.8% remained event-free at 2 years
• 25% reduced risk of death vs neoadjuvant chemotherapy with radical cystectomy (HR, 0.75; 95% CI, 0.59-0.93; P = .0106)
• 82.2% vs 75.2% OS rate at 2 years
• Median survival not reached in the treatment and comparator arms

Approximately 25% of patients who have bladder cancer have MIBC,⁴ for which standard curative-intent treatments are neoadjuvant chemotherapy and radical cystectomy.

Durvalumab is also approved to treat unresectable stage III non–small cell lung cancer (NSCLC) that has not progressed after concurrent platinum chemotherapy and radiation, in combination with tremelimumab-actl and platinum-based chemotherapy against NSCLC that lacks EGFR mutations or ALK aberrations, in the first line for extensive-stage small cell lung cancer (SCLC) with etoposide and carboplatin or cisplatin, with gemcitabine and cisplatin for locally advanced or metastatic biliary tract cancer (BTC), and with tremelimumab-actl for unresectable hepatocellular carcinoma (uHCC).⁵

Common adverse reactions (> 20%) associated with durvalumab vary based on the setting:

• Monotherapy for stage 3 NSCLC: cough, fatigue, pneumonitis/radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash
• With platinum-based chemotherapy for extensive-stage SCLC: nausea, fatigue/asthenia, and alopecia
• With gemcitabine and cisplatin for BTC: fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia
• With tremelimumab-actl for uHCC: rash, diarrhea, fatigue, pruritis, musculoskeletal pain, and abdominal pain
• With tremelimumab-actl and platinum-based chemotherapy for metastatic NSCLC: nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea

The newest data do not show new safety signals emerging in the neoadjuvant or adjuvant setting, and that durvalumab plus neoadjuvant chemotherapy had a safety profile consistent with the combination. Any immune-mediated adverse events for manageable, low grade, and consistent with durvalumab’s known safety profile.

NCCN Recommendation⁶

Also based on NIAGARA data, the National Comprehensive Cancer Network (NCCN) Clinical Practical Guidelines in Oncology added perioperative durvalumab, neoadjuvant cisplatin-based chemotherapy, and cystectomy at a Category 1 Recommendation in February 2025 for patients with MIBC.

References

1. Imfinzi approved in the US as the first and only perioperative immunotherapy for patients with muscle-invasive bladder cancer. News release. AstraZeneca; March 31, 2025. Accessed March 31, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-approved-in-the-us-for-bladder-cancer.html

2. FDA approves durvalumab for muscle invasive bladder cancer. News release. FDA; March 28, 2025. Accessed March 31, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-muscle-invasive-bladder-cancer

3. Durvalumab+ gemcitabine/cisplatin (neoadjuvant treatment) and durvalumab (adjuvant treatment) in patients with MIBC (NIAGARA). ClinicalTrials.gov. Updated March 25, 2025. Accessed March 31, 2025. https://clinicaltrials.gov/study/NCT03732677

4. Imfinzi granted priority review in the US for patients with muscle-invasive bladder cancer. News release. AstraZeneca; December 6, 2024. Accessed March 31, 2025. https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-granted-priority-review-in-the-us-for-patients-with-muscle-invasive-bladder-cancer.html

5. Imfinzi. Prescribing information. AstraZeneca; 2022. Accessed March 31, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761069s033lbl.pdf#:~:text=IMFINZI%20is%20indicated%20for%20the%20treatment%20of,following%20concurrent%20platinum%2Dbased%20chemotherapy%20and%20radiation%20therapy.&text=IMFINZI%2C%20in%20combination%20with%20gemcitabine%20and%20cisplatin%2C,advanced%20or%20metastatic%20biliary%20tract%20cancer%20(BTC)

6. NCCN clinical practice guidelines in oncology (NCCN guidelines): bladder cancer. Version 1.2025. NCCN. March 25, 2025. Accessed March 31, 2025. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf