Positive results from the NIAGARA Phase III trial showed AstraZeneca's Imfinzi (durvalumab) in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival (EFS) and the key secondary endpoint of overall survival (OS) versus neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC). Patients were treated with Imfinzi in combination with neoadjuvant chemotherapy before radical cystectomy (surgery to remove the bladder) followed by Imfinzi as adjuvant monotherapy.

These results will be presented today during a Presidential Symposium at the 2024 European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain (abstract #LBA5) and simultaneously published in The New England Journal of Medicine (https://www.nejm.org/).

In a planned interim analysis, 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 (based on EFS hazard ratio [HR] of 0.68; 95% confidence interval [CI] 0.56-0.82; p<0.0001). Estimated median EFS was not yet reached for the Imfinzi arm versus 46.1 months for the comparator arm. An estimated 67.8% of patients treated with the Imfinzi regimen were event free at two years compared to 59.8% in the comparator arm.

Results from the key secondary endpoint of OS showed the Imfinzi perioperative regimen reduced the risk of death by 25% versus neoadjuvant chemotherapy with radical cystectomy (based on OS HR of 0.75; 95% CI 0.59-0.93; p=0.0106). Median survival was not yet reached for either arm. An estimated 82.2% of patients treated with the Imfinzi regimen were alive at two years compared to 75.2% in the comparator arm.

Professor Thomas Powles, MD, Director of Barts Cancer Centre (QMUL), London, UK, and principal investigator in the NIAGARA trial, said: "Neoadjuvant chemotherapy with bladder removal has been the mainstay of treatment for patients with muscle-invasive bladder cancer for nearly twenty years; however, half of patients still go on to suffer a devastating recurrence. Adding durvalumab before and after surgery significantly reduced the chance of recurrence and extended survival, a significant advance with the potential to transform the standard of care for these patients who desperately need better outcomes."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The NIAGARA data showed compelling improvements in both event-free survival and overall survival, with more than 80 per cent of patients treated with the Imfinzi perioperative regimen alive at two years. This is the first immunotherapy regimen to significantly extend overall survival in muscle-invasive bladder cancer, and it further validates our strategy to move cancer treatment as early as possible to maximise benefit for patients."

Summary of results: NIAGARA

[][][]
  Imfinzi-based Neoadjuvant
regimen chemotherapy
(n=533) (n=530)
EFS
Number of patients 187 (35.1) 246 (46.4)
with event (%)
Median EFS (95% CI) NR (NR-NR) 46.1 (32.2
(in months) -NR)
HR (95% CI) 0.68 (0.56
-0.82)
p-value <0.0001
EFS rate at 12 76.0 69.9
months (%)
EFS rate at 24 67.8 59.8
months (%)
OS
Number of deaths, n 136 (25.5) 169 (31.9)
(%)
HR (95% CI) 0.75 (0.59
-0.93)
Stratified log-rank 0.0106
p-value
OS rate at 12 89.5 86.5
months (%)
OS rate at 24 82.2 75.2
months (%)
[i]With the
observed number of
events, the
boundary for
declaring
statistical
significance was
0.04123 for a 4.9%
overall 2-sided
alpha[ii]With the
observed number of
events, the
boundary for
declaring
statistical
significance was
0.01543 for a 4.9%
overall 2-sided
alpha. Data cutoff
24 Apr
2024.[iii]Unplanned
pCR re-analysis
(DCO Apr 24),
including 59
samples omitted
from formal pCR
analysis.NR, not
reached

Imfinzi was generally well tolerated and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding Imfinzi to 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. Grade 3 and 4 adverse events due to any cause occurred in 69% of patients treated with Imfinzi and 68% of patients treated with neoadjuvant chemotherapy.

In addition to NIAGARA, Imfinzi is also being tested across early- and late-stage bladder cancer in various treatment combinations, including in non-muscle invasive disease (POTOMAC), patients with MIBC who are cisplatin-ineligible or refusing cisplatin (VOLGA) and locally advanced or metastatic disease (NILE).

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]

MIBC, named for its growth into the muscle wall of the bladder, accounts for about a quarter of all bladder cancer cases.[3,4] In the MIBC setting, approximately 117,000 patients are treated with current standard of care.[5] Standard treatment includes neoadjuvant chemotherapy and radical cystectomy.[6] However, even after cystectomy, patients experience high rates of recurrence and a poor prognosis.[6] Approximately 50% of patients who undergo bladder removal surgery experience disease recurrence.[6] Treatment options that prevent disease recurrence after surgery are critically needed.   

NIAGARA   

NIAGARA is a randomised, open-label, multi-centre, global Phase III trial evaluating Imfinzi as treatment for patients with MIBC before and after radical cystectomy. In the trial, 1,063 patients were randomised to receive Imfinzi plus chemotherapy or chemotherapy alone prior to cystectomy, followed by Imfinzi or no further treatment after surgery.  

The trial is being conducted at 192 centres across 22 countries including in the US, Canada, Europe, Australia and Asia. Its dual primary endpoints are EFS, defined as the time from treatment randomisation to an event like tumour recurrence or progression and pathologic complete response. 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 tumour's immune-evading tactics and releasing the inhibition of immune responses. 

Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy. Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, in combination with chemotherapy for the treatment of extensive-stage small cell lung cancer (SCLC) and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC.  

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 Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU. Imfinzi is also approved in combination with chemotherapy (carboplatin and paclitaxel) followed by Imfinzi monotherapy in primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) in the US. In the EU, Imfinzi plus chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient disease advanced or recurrent endometrial cancer, and Imfinzi plus chemotherapy followed by Imfinzi alone is approved for patients with dMMR disease. 

Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, breast cancer, bladder cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours.   

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-tumour immune response and stimulate the body's immune system to attack tumours. 

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 programme, 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 catalyse 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 (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com (http://www.astrazeneca.com/) and follow the Company on social media @AstraZeneca (https://www.linkedin.com/company/astrazeneca/).

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References

1. 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 September 2024.
2. American Cancer Society. What Is Bladder Cancer? Available at: https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html. Accessed September 2024.
3. Burger M, et al. Epidemiology and Risk Factors of Urothelial Bladder Cancer. Eur Urol. 2013;63(2):234-241.
4. 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 September 2024.
5. Cerner CancerMPact database. Accessed September 2024. Reflects epidemiology estimates across G8 countries (US, EU, Japan, China).
6. Witjes JA, et al. EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. Eur Urol. 2021;1-94.