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Phase 3 Study Shows XTANDI® (enzalutamide) plus Leuprolide Significantly Improves Metastasis-Free Survival in Men with Nonmetastatic Prostate Cancer

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Addlestone UK, 17 March, 2023 –Astellas Pharma Ltd. (“Astellas”) today announced positive topline results from the Phase 3 EMBARK trial evaluating XTANDI® (enzalutamide) in men 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). Patients enrolled in the trial were randomised to one of three study arms: XTANDI plus leuprolide, placebo plus leuprolide, or XTANDI monotherapy. 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 placebo plus leuprolide.  


At the time of the analysis, a positive trend in the key secondary endpoint of overall survival (OS) was also observed, but these data were not yet mature. Patients in the trial will be followed for a subsequent final OS analysis. The study also met a key secondary endpoint with a statistically significant and clinically meaningful improvement in MFS for patients treated with XTANDI monotherapy versus placebo plus leuprolide. Additional key secondary endpoints reached statistical significance, including time to PSA progression and time to first use of new antineoplastic therapy. Other secondary endpoints are being analysed. No new safety signals have been observed to date in the preliminary safety analysis, which is consistent with the established safety profile of XTANDI.


“While current treatment options for localised prostate cancer are intended to be curative, some men remain at higher risk for biochemical recurrence following primary treatment, which may result in metastases,” said Ahsan Arozullah, M.D., MPH, Senior Vice President and Head of Development Therapeutic Areas, Astellas. “The EMBARK trial is the first study to demonstrate a statistically significant improvement in MFS using the combination of XTANDI plus leuprolide in men with this stage of disease.”


“The topline findings from EMBARK are highly encouraging.” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development. “We look forward engaging with health authorities to potentially bring XTANDI to men with non-metastatic hormone sensitive prostate cancer and high-risk biochemical recurrence.” 


Detailed results from EMBARK will be presented at a future medical meeting. These data will also be discussed with regulatory authorities, including the U.S. Food and Drug Administration (FDA), to support a potential regulatory submission for XTANDI in this indication.






The Phase 3, randomised, 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) and high-risk biochemical recurrence (BCR) at sites in the United States, Canada, Europe, South America, and the Asia-Pacific region. Patients who were considered high-risk BCR 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 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 randomised to receive enzalutamide 160 mg daily plus leuprolide, enzalutamide 160 mg as a monotherapy, or placebo plus leuprolide.


The primary endpoint of the trial was metastasis-free survival (MFS) for enzalutamide plus leuprolide and placebo plus leuprolide. MFS is defined as the duration of time in months between randomisation and the earliest objective evidence of radiographic progression by central imaging or death. For more information on the EMBARK (NCT02319837) trial go to


XTANDI has not been approved for the treatment of patients with nmHSPC and high-risk BCR.


About Non-Metastatic Hormone-Sensitive Prostate Cancer and High-Risk Biochemical Recurrence 

Non-metastatic hormone- (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC) means there is no clinically detectable evidence of the cancer spreading to other parts of the body (metastases) and the cancer still responds to medical or surgical treatment to lower testosterone levels.[i],[ii] 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.[iii] About 9 out of 10 men with high-risk BCR will develop metastatic disease, and 1 in 3 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 and high-risk BCR are those initially treated by radical prostatectomy or radiotherapy, or both, with a PSA doubling time ≤ 9 months. High-risk BCR patients with a PSA doubling time of ≤ 9 months have a higher risk of metastases and death.[iv]


About XTANDI® (enzalutamide)


Enzalutamide is an androgen receptor signaling inhibitor indicated in the United Kingdom for the treatment of adult men with:[v]


  1. Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT).
  2. High-risk non-metastatic castration-resistant prostate cancer (CRPC).
  3. Metastatic CRPC who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated. It is also indicated in adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy.



[i] Prostate Cancer: Types of Treatment (12-2022). Accessed March 16, 2023.

[ii] American Society of Clinical Oncology. ASCO Answers: Prostate Cancer (2021). Accessed March 16, 2023.

[iii] 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.

[iv] 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

[v] Xtandi (enzalutamide) Summary of Product Characteristics. Accessed March 16 2023

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