IMFINZI reduced the risk of distant metastases and death from bladder cancer vs. neoadjuvant chemotherapy alone
WILMINGTON, DE, USA I February 14, 2025 I Results from a post-hoc exploratory subgroup analysis from the NIAGARA Phase III trial showed AstraZeneca’s IMFINZI®(durvalumab), administered perioperatively in combination with neoadjuvant chemotherapy, demonstrated improvements in event-free survival (EFS) and overall survival (OS) versus neoadjuvant chemotherapy with radical cystectomy alone in patients with or without a pathologic complete response (pCR) in muscle-invasive bladder cancer (MIBC). Patients were treated with four cycles of IMFINZI in combination with neoadjuvant chemotherapy before radical cystectomy (surgery to remove the bladder) followed by eight cycles of IMFINZI monotherapy.
These new data were presented today at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in San Francisco, California (abstract #659).
In NIAGARA, treatment with the IMFINZI perioperative regimen improved EFS and OS versus the comparator arm both in patients who achieved pCR and those who did not. This regimen reduced the risk of disease progression, recurrence, not undergoing surgery, or death by 42% in patients who achieved pCR and by 23% in those who did not; and reduced the risk of death by 28% in patients who achieved pCR and by 16% in those who did not (see data table below for details).
The IMFINZIperioperative regimen also improved metastasis-free survival (MFS) and disease-specific survival (DSS), two secondary endpoints, versus the comparator arm in the intent-to-treat (ITT) population. This regimen reduced the risk of developing distant metastases or death by 33% and the risk of death specifically due to bladder cancer by 31% versus the comparator arm (see data table below for details).
Matthew ND. Galsky, Lillian and Howard Stratton Professor of Medicine, Director of Genitourinary Medical Oncology, The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, and NIAGARA Investigator and Steering Committee member, said: “These NIAGARA data confirm the compelling efficacy of the durvalumab perioperative regimen in muscle-invasive bladder cancer, and importantly, show this regimen improved outcomes regardless of whether patients achieved a pathologic complete response. This insight, together with the data showing the durvalumab perioperative regimen extended the time patients live before distant metastases develop, is favorable news for patients with muscle-invasive bladder cancer who are in need of better treatment options.”
Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “NIAGARA was the first Phase III trial of a perioperative immunotherapy regimen in muscle-invasive bladder cancer to show statistically significant and clinically meaningful improvements in event-free and overall survival. The 33 percent reduction in the risk of distant metastases, which are associated with a poorer prognosis, further reinforces the potential of perioperative IMFINZIto become a new standard of care in this setting.”
These new data build on findings presented at the European Society for Medical Oncology (ESMO) Congress and published in The New England Journal of Medicine which showed NIAGARA met the primary endpoint of EFS and the key secondary endpoint of OS. In the ITT population, patients treated with the IMFINZI perioperative regimen showed a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death versus the comparator arm, as well as a 25% reduction in the risk of death. There was also a 10% improvement in the pCR rate versus the comparator arm.
Summary of exploratory post-hoc analysis: NIAGARA
| Patients with pCR | Patients without pCR | ITT population | ||||
| IMFINZI- based regimen (n=199) | Neoadjuvant chemotherapy (n=146) | IMFINZI- based regimen (n=334) | Neoadjuvant chemotherapy (n=384) | IMFINZI- based regimen (n=533) | Neoadjuvant chemotherapy (n=530) | |
| pCRi | ||||||
| pCR rate (%) | – | – | – | – | 37.3 | 27.5 |
| p-valueii | – | – | 0.0005 | |||
| EFSi | ||||||
| EFS rate, | ||||||
| 24 months | 92.1 | 85.8 | 53.3 | 49.5 | 67.8 | 59.8 |
| (%) | ||||||
| HR (95% | 0.58 | 0.77 | 0.68 | |||
| CI) | (0.33-1.00) | (0.63-0.95) | (0.56-0.82) | |||
| OSi | ||||||
| OS rate, 24 months (%) | 95.5 | 91.1 | 74.1 | 68.9 | 82.2 | 75.2 |
| HR (95% | 0.72 | 0.84 | 0.75 | |||
| CI) | (0.37-1.43) | (0.66-1.07) | (0.59-0.93) | |||
| i Data cut-off: April 29, 2024 | ||||||
| ii Nominal p-value | ||||||
Summary of additional secondary endpoint outcomes (ITT): NIAGARA
| IMFINZI-based regimen (n=533) | Neoadjuvant chemotherapy (n=530) | |
| MFSi | ||
| MFS rate, 24 months (%) | 75.1 | 65.1 |
| Number of MFS events | 152 | 201 |
| (%) | (28.5) | (37.9) |
| Median MFS (95% CI) (in | NRii | NRii |
| months) | (NRii-NRii) | (48.0-NRii) |
| HR (95% CI) | 0.67 (0.54-0.83) | |
| DSSi | ||
| DSS rate, 24 months (%) | 89.2 | 82.2 |
| Number of deaths due to | 85 | 114 |
| bladder cancer (%) | (15.9) | (21.5) |
| Median DSS (95% CI) (in | NRii | NRii |
| months) | (NRii-NRii) | (NRii-NRii) |
| HR (95% CI) | 0.69 (0.52-0.91) | |
| i Data cut-off: April 29, 2024 | ||
| ii NR, not reached | ||
IMFINZI was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding IMFINZIto neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery compared to neoadjuvant chemotherapy alone. Immune-mediated adverse events (imAEs) were consistent with the known profile of IMFINZI, manageable and mostly low-grade.
Perioperative IMFINZI in combination with neoadjuvant chemotherapy was granted Priority Review in the US in December 2024 for the treatment of patients with MIBC.Regulatory applications are also currently under review in the European Union (EU), Japan and several other countries based on the NIAGARA trial.
Indications:
IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).
IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.
IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.
IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).
IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).
IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).
IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).
IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).
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Notes
Muscle-invasive bladder cancer
Bladder cancer is the 9th most common cancer in the world, with more than 614,000 patients diagnosed each year.1 The most common type of bladder cancer is urothelial carcinoma, which begins in the urothelial cells of the urinary tract.2 Approximately one in four patients with bladder cancer has evidence of the tumor invading the muscle wall of the bladder (without distant metastases), known as MIBC.3-4
In MIBC, a curative-intent setting, approximately 117,000 patients are treated with the current standard of care, which includes neoadjuvant chemotherapy and radical cystectomy.5-6 However, even after cystectomy, approximately 50% of patients experience disease recurrence and have a poor prognosis.6 Treatment options that prevent disease recurrence after surgery are critically needed in this curative-intent setting.
NIAGARA
NIAGARA is a randomized, open-label, multi-center, global Phase III trial evaluating perioperative IMFINZI as treatment for patients with MIBC before and after radical cystectomy. In the trial, 1,063 patients were randomized to receive IMFINZI plus neoadjuvant chemotherapy prior to cystectomy followed by IMFINZI, or neoadjuvant chemotherapy alone prior to cystectomy with no further treatment after surgery. NIAGARA is the largest global Phase III trial in this setting.
The trial is being conducted at 192 centers across 22 countries including in North America, South America, Europe, Australia and Asia. Its dual primary endpoints are EFS and pCR, the latter defined as the proportion of patients with no detectable cancer cells (T0N0M0) at the time of cystectomy. Key secondary endpoints are OS and safety.
IMFINZI
IMFINZI® (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.
IMFINZI is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, IMFINZI is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of IMJUDO® (tremelimumab-actl) and chemotherapy for the treatment of metastatic NSCLC. IMFINZIis also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC.
In addition to its indications in lung cancers, IMFINZI is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with IMJUDOin unresectable hepatocellular carcinoma (HCC). IMFINZI is also approved as a monotherapy in unresectable HCC in Japan and the EU.
IMFINZIis also approved in combination with chemotherapy (carboplatin and paclitaxel) followed by IMFINZImonotherapy in primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) in the US. In the EU, IMFINZIplus chemotherapy followed by olaparib and IMFINZIis approved for patients with mismatch repair proficient (pMMR) advanced or recurrent endometrial cancer, and IMFINZI plus chemotherapy followed by IMFINZIalone is approved for patients with dMMR disease. In Japan, IMFINZI plus chemotherapy followed by IMFINZImonotherapy has also been approved as 1st-line treatment in primary advanced or recurrent endometrial cancer, and IMFINZI plus chemotherapy followed by IMFINZI and olaparib has been approved for patients with pMMR disease.
Since the first approval in May 2017, more than 374,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumors.
AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumor immune response and stimulate the body’s immune system to attack tumors.
AstraZeneca strives to redefine cancer care and help transform outcomes for patients with IMFINZI as a monotherapy and in combination with IMJUDO as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers.
AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical program, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on socia media @AstraZeneca.
References
- World Health Organization. International Agency for Research on Cancer. Bladder Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/30-bladder-fact-sheet.pdf. Accessed February 2025.
- American Cancer Society. What Is Bladder Cancer? Available at: https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html. Accessed February 2025.
- Burger M, et al. Epidemiology and Risk Factors of Urothelial Bladder Cancer. Eur Urol. 2013;63(2):234-241.
- National Collaborating Centre for Cancer. Bladder Cancer: Diagnosis and Management. London: National Institute for Health and Care Excellence (NICE). Available at: https://www.ncbi.nlm.nih.gov/books/NBK356289. Accessed February 2025.
- Cerner CancerMPact database. Accessed February 2024. Reflects epidemiology estimates across G8 countries (US, EU, Japan, China).
- Witjes JA, et al. EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. Eur Urol. 2021;1-94.
SOURCE: AstraZeneca
