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The probability of survival at 8 years was an unprecedented 78.9% with XTANDI plus leuprolide versus 69.5% with leuprolide, in men with non-metastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence1
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XTANDI is the first and only androgen receptor inhibitor-based regimen to demonstrate overall survival benefit in this patient population, supporting its earlier use in this setting
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Final results from the Phase 3 EMBARK study are being presented in a late-breaking oral session at ESMO 2025 and simultaneouslypublished in The New England Journal of Medicine
Sunday, October 19, 2025 - NEW YORK & NORTHBROOK, Ill.--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) and Astellas Pharma U.S. Inc. (Head of Commercial: Mike Petroutsas, "Astellas") today announced final overall survival (OS) results from the Phase 3 EMBARK study evaluating XTANDI® (enzalutamide), in combination with leuprolide and as monotherapy, in men with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as nonmetastatic castration-sensitive prostate cancer or nmCSPC) with biochemical recurrence (BCR) at high risk for metastasis. For the key secondary endpoint of OS, XTANDI plus leuprolide reduced the risk of death by 40.3% compared to leuprolide alone (Hazard Ratio [HR]: 0.597; 95% Confidence Interval [CI], 0.444-0.804; p=0.0006), making this the first and only androgen receptor inhibitor-based regimen to demonstrate an OS benefit in nmHSPC with high-risk BCR.1 The 8-year overall survival was 78.9% (95% CI, 73.9% to 83.1%) among patients receiving XTANDI plus leuprolide and 69.5% (95% CI, 64.0% to 74.3%) among patients taking leuprolide alone.1 A numerical improvement in OS with XTANDI as monotherapy compared to leuprolide alone (HR: 0.83 [95% CI, 0.63-1.095; p=0.1867) did not reach statistical significance.1 These data are being presented today in an oral presentation at the European Society for Medical Oncology (ESMO) Congress in Berlin, Germany and have been simultaneously published in The New England Journal of Medicine.
“These results highlight the central role of enzalutamide in extending survival for men with conventional imaging negative HSPC with high-risk BCR,” said Stephen J. Freedland, M.D., Director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai and Associate Director for Training and Education at the Samuel Oschin Comprehensive Cancer Institute. “These data reinforce the benefits of earlier treatment initiation with enzalutamide.”
The median follow up time was 94.2 months for XTANDI in combination with leuprolide, 94 months for leuprolide only, and 93.8 months in the monotherapy XTANDI group.1
The safety profile of XTANDI was consistent with that observed at the primary EMBARK analysis, and no new safety signals were identified. The most common adverse events (occurring in ≥10% of patients) in the XTANDI combination group were hot flashes and fatigue. The most common adverse events in the XTANDI monotherapy group were gynecomastia, hot flashes, and fatigue.1,2
"With up to 90 percent of men with high-risk BCR developing metastatic disease, early intervention with effective therapy is critical,”3 said Johanna Bendell, M.D., Chief Development Officer, Oncology, Pfizer. “The final analysis from EMBARK shows that XTANDI plus leuprolide improved outcomes and extended lives for men facing high-risk BCR after local therapy with curative intent.”
Among men who have undergone definitive prostate cancer treatment, including radical prostatectomy, radiotherapy or both, an estimated 20-40% will experience BCR within 10 years.4 About nine out of 10 men with high-risk BCR will develop metastatic disease, and one in three will die as a result of their metastatic prostate cancer.3
“This marks the eighth publication of XTANDI data in The New England Journal of Medicine, further demonstrating XTANDI’s profound impact on clinical outcomes in men with certain types of advanced prostate cancer,” said Shontelle Dodson, Executive Vice President, Head of Medical Affairs, Astellas. “These findings reinforce XTANDI’s position as a cornerstone therapy in the proactive management of these patients.”
The EMBARK trial primary analysis was previously reported in The New England Journal of Medicine in 2023, demonstrating that the study met its primary endpoint with a statistically significant and clinically meaningful improvement in metastasis-free survival (MFS) for patients treated with XTANDI plus leuprolide versus leuprolide alone (HR: 0.42 [95% CI, 0.30-0.61]; p<0.001). Additionally, MFS for XTANDI monotherapy was superior to treatment with leuprolide alone (HR: 0.63 [95% CI, 0.46-0.87]; p=0.005). Of note, the MFS for XTANDI single agent was a secondary endpoint.2
XTANDI is approved for one or more indications in more than 80 countries, including the United States, European Union, and Japan. Earlier approvals were for castration-resistant prostate cancer and metastatic castration-sensitive (hormone-sensitive) prostate cancer. It was then approved for patients with nmCSPC with BCR at high risk for metastasis in 2023 based on improved metastasis-free survival comparing the combination of enzalutamide with leuprolide vs leuprolide alone, as well as enzalutamide monotherapy vs leuprolide alone.
Descriptive updates of multiple secondary and exploratory endpoints (time to new antineoplastic therapy, time to first symptomatic skeletal events, and time to progression on subsequent therapy) were consistent with the primary analyses announced based on the MFS data cutoff in 2023.1
About EMBARK2
This Phase 3, randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,068 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as non-metastatic castration-sensitive prostate cancer or nmCSPC) with high-risk biochemical recurrence (BCR) at sites in the United States, Canada, Europe, South America, and the Asia-Pacific region. Patients considered to have high-risk BCR disease had a prostate-specific antigen (PSA) doubling time ≤ 9 months, serum testosterone ≥ 150 ng/dL (5.2 nmol/L), and screening PSA by the central laboratory ≥ 1 ng/mL if they had had a radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer or at least 2 ng/mL above the nadir if they had radiotherapy only as primary treatment for prostate cancer. Patients in the EMBARK trial were randomized to receive enzalutamide 160 mg daily plus leuprolide, enzalutamide 160 mg as monotherapy, or leuprolide alone.
The primary results from the EMBARK trial were published in the New England Journal of Medicinein 2023. The primary endpoint of the trial was metastasis-free survival (MFS) for enzalutamide plus leuprolide versus leuprolide alone. MFS is defined as the duration of time between randomization and the earliest objective evidence of radiographic progression by central imaging or death.
For more information on the EMBARK (NCT02319837) trial go to www.clinicaltrials.gov.
About Non-Metastatic Hormone-Sensitive Prostate Cancer with High-Risk Biochemical Recurrence
Non-metastatic hormone- (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC) means there is no detectable evidence of the cancer spreading to distant parts of the body (metastases) with conventional radiological methods (CT/MRI) and the cancer still responds to medical or surgical treatment to lower testosterone levels.5,6 Of men who have undergone definitive prostate cancer treatment, including radical prostatectomy, radiotherapy, or both, an estimated 20-40% will experience a biochemical recurrence (BCR) within 10 years.4 About nine out of 10 men with high-risk BCR will develop metastatic disease, and one in three will die as a result of the recurrence.3 The EMBARK trial focused on men with high-risk BCR. Per the EMBARK protocol, patients with nmHSPC with high-risk BCR are those initially treated by radical prostatectomy or radiotherapy, or both, with a PSA doubling time ≤ 9 months. Patients with nmCSPC who experience BCR after local therapy may be at a higher risk of metastases and death if their PSA doubling time is ≤ 9 months.7
About XTANDI® (enzalutamide)
XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence (BCR). XTANDI is currently approved for one or more of these indications in more than 80 countries, including in the United States, European Union and Japan. Over 1.5 million patients have been treated with XTANDI globally.8
About Astellas
Astellas is a global life sciences company committed to turning innovative science into VALUE for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women's health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need. Learn more at www.astellas.com.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
About the Pfizer/Astellas Collaboration
In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE: PFE), and Astellas (TSE: 4503) entered into a global agreement to jointly develop and commercialize XTANDI (enzalutamide). The companies jointly commercialize XTANDI in the United States, and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States.
References
1 Shore, D. et al. Overall survival with enzalutamide in biochemically recurrent prostate cancer. Presented at the 2025 ESMO Annual Meeting.
2 Freedland, Stephen J. et al. “Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer.” N Engl J Med 2023;389:1453-1465. DOI: 10.1056/NEJMoa2303974
3 Antonarakis, Emmanuel S et al. The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up. BJU international vol. 109,1 (2012): 32-9. doi:10.1111/j.1464-410X.2011.10422
4 Ward JF, Moul JW. Rising prostate-specific antigen after primary prostate cancer therapy. Nat Clin Pract Urol. 2005 Apr;2(4):174-82. doi: 10.1038/ncpuro0145. PMID: 16474760.
5 Cancer.net. Prostate Cancer: Types of Treatment (11-2023). https://www.cancer.net/cancer-types/prostate-cancer/types-treatment. Accessed September 19, 2025.
6 American Society of Clinical Oncology. ASCO Answers: Prostate Cancer (2023).
7 Paller, Channing J et al. Management of patients with biochemical recurrence after local therapy for prostate cancer. Hematology/oncology clinics of North America vol. 27,6 (2013): 1205-19, viii. doi:10.1016/j.hoc.2013.08.005
8 Astellas. Data on file. XTANDI patient. March 2025.