Key Takeaways
Xtandi plus leuprolide significantly improves overall survival: In patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC) and high-risk biochemical recurrence, the combination reduced the risk of metastasis or death by 58% versus leuprolide alone.
Xtandi monotherapy shows a favorable survival trend: This trend supports the drug’s potential as an effective treatment option for this patient population, although it did not reach statistical significance.
No new safety signals observed: Common adverse events were consistent with the combination’s known safety profiles, reinforcing the established safety and tolerability of Xtandi.
Results from the Phase III EMBARK trial show that Astellas and Pfizer’s Xtandi (enzalutamide), in combination with leuprolide, significantly improves overall survival (OS) in men with non-metastatic hormone-sensitive prostate cancer (nmHSPC) and high-risk biochemical recurrence (BCR). Xtandi also demonstrated a favorable OS trend as a monotherapy, although it did not reach statistical significance, according to the companies.1
How did Xtandi Perform in Combination and as a Monotherapy in the EMBARK Trial?
“These data demonstrate that treatment with Xtandi can extend life for men with nmHSPC and high-risk BCR who have relapsed after initial curative-intent therapy with prostatectomy, radiation therapy or both, further validating EMBARK’s metastasis-free survival (MFS) data,” said Neal Shore, MD, FACS, START Carolinas/Carolina Urologic Research Center, in a press release. “While men with nmHSPC with high-risk BCR now have expanded treatment choices, these results demonstrate a clear clinical benefit, including both MFS and OS, supporting the clinical practice of initiating Xtandi for these patients.”
Key Design and Endpoints of the EMBARK Trial
- The randomized, double-blind, placebo-controlled, multinational EMBARK trial evaluated Xtandi plus leuprolide compared to placebo plus leuprolide in 1,068 men with nmHSPC with high risk BCR.
- Patients were randomly assigned to receive either 160 mg of Xtandi plus leuprolide daily, 160 mg of Xtandi as a monotherapy, or placebo plus leuprolide.
- The primary endpoint of the trial was MFS. A key secondary endpoint was a statistically significant and clinically meaningful improvement in OS.
Survival Outcomes and Efficacy Results
- Results from an early analysis showed that after a median follow-up for 60.7 months, the five-year MFS rates were 87.3% for the combination group, 71.4% for patients treated with leuprolide alone, and 80% for those in the Xtandi monotherapy group.
- Patients in the combination group demonstrated a 58% reduction in the risk of metastasis or death versus leuprolide alone (HR, 0.42; P<0.001), while Xtandi monotherapy reduced that risk by 37% compared to leuprolide alone (HR, 0.63; P=0.005).2
Safety Profile and Adverse Events (AEs)
- Common AEs in the combination group and leuprolide-alone group were hot flashes and fatigue.
- In the leuprolide monotherapy group, the most common AEs were gynecomastia, hot flashes, and fatigue.
- No new safety signals were identified, and the results remained consistent with the previously established safety profile for Xtandi.1
Broader Clinical Impact of Xtandi
“Xtandi is the only androgen receptor inhibitor-based regimen to demonstrate a survival benefit in metastatic HSPC and nmHSPC with high-risk BCR, as well as castration-resistant prostate cancer, highlighting its significant patient impact in advanced prostate cancer,” said Johanna Bendell, MD, oncology chief development officer, Pfizer, in the press release. “These positive results add to the robust clinical support for the use of Xtandi and broaden clinical confidence, offering men with high-risk BCR evidence that they might live longer when they start Xtandi early.”
Prostate Cancer Prevalence and Ongoing Commitment
According to the American Cancer Society, prostate cancer is the most common form of the disease in men in the United States, outside of skin cancers. On average, every one out of eight men in the United States will be diagnosed with prostate cancer during their lifetime. It is also the second leading cause of cancer-related deaths in men in the United States, with lung cancer being the first.3
“Over 1.5 million men with advanced prostate cancer around the world have benefited from treatment with Xtandi since its initial approval in 2012,” said Shontelle Dodson, EVP, head, medical affairs, Astellas, in the press release. “The scope and rigor of the EMBARK trial exemplify Astellas’ and Pfizer’s longstanding commitment to the prostate cancer community, and we look forward to sharing detailed findings in a future scientific forum.”
References
- XTANDI® Plus Leuprolide Significantly Improves Survival Outcomes in Men with Non-Metastatic Hormone-Sensitive Prostate Cancer with High-Risk Biochemical Recurrence. Pfizer. July 10, 2025. Accessed July 10, 2025. https://www.pfizer.com/news/press-release/press-release-detail/xtandir-plus-leuprolide-significantly-improves-survival
- Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. The New England Journal of Medicine. Accessed July 10, 2025. https://www.nejm.org/doi/10.1056/NEJMoa2303974?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
- Key Statistics for Prostate Cancer. American Cancer Society. Accessed July 10, 2025, https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html
