XTANDI Delivers Sustained Five-Year Survival Benefit in Metastatic Hormone-Sensitive Prostate Cancer: Landmark Findings from ARCHES and ENZAMET Trials Presented at ASCO 2025
Astellas Pharma Inc. and Pfizer Inc. have announced compelling new data from the long-term extension of the Phase 3 ARCHES trial, revealing significant survival benefits for men with metastatic hormone-sensitive prostate cancer (mHSPC) treated with XTANDI™ (enzalutamide) in combination with androgen deprivation therapy (ADT). The findings, which underscore the growing role of enzalutamide in the treatment paradigm for advanced prostate cancer, will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting during an oral presentation on June 3 in Chicago.
The five-year follow-up data demonstrate that the combination of XTANDI and ADT significantly reduces the risk of death by 30% compared to ADT alone, with approximately two-thirds of treated patients still alive at the five-year mark. These results, based on data from the global ARCHES study (NCT02677896), highlight a remarkable improvement over the historical outlook for mHSPC patients, who previously faced low long-term survival probabilities.
A New Standard for Long-Term Survival
Dr. Andrew J. Armstrong, Director of Research at the Center for Prostate & Urologic Cancers at Duke Cancer Institute and primary investigator for the ARCHES study, emphasized the clinical significance of the findings.
“Historically, the likelihood of survival at five years for men with metastatic hormone-sensitive prostate cancer was low,” Dr. Armstrong said. “But with advancements in initial treatment intensification like what we’ve seen with XTANDI, this is now becoming the standard.”
The study’s five-year analysis showed a 13% absolute improvement in overall survival and a 30% relative risk reduction. These benefits were consistent across multiple patient subgroups, including those with both high and low disease burden, as well as patients with or without prior treatment with docetaxel—a commonly used chemotherapy agent in prostate cancer.
In men with high-volume disease, the addition of XTANDI to ADT extended median overall survival by 36 months (HR: 0.70; 95% CI: 0.56–0.88). For those with low-volume disease, the hazard ratio was 0.71 (95% CI: 0.49–1.05), while patients with previous docetaxel exposure had a hazard ratio of 0.67 (95% CI: 0.43–1.05). Among patients without prior docetaxel, the survival benefit remained substantial (HR: 0.71; 95% CI: 0.57–0.88).
Adverse events reported over the five-year follow-up remained consistent with previous analyses of the ARCHES study, and no new safety concerns emerged, further supporting the long-term tolerability of XTANDI.
XTANDI Reinforces Its Role in Advanced Prostate Cancer
Shontelle Dodson, Executive Vice President and Head of Medical Affairs at Astellas, described the results as a reaffirmation of XTANDI’s growing legacy in prostate cancer care.
“The survival benefits of intervention with XTANDI in advanced prostate cancer are well-recognized,” Dodson said. “The collective – and growing – body of data for XTANDI continues to reinforce its long-term efficacy and patient impact in prostate cancer, including in the metastatic setting.”
Pfizer’s Oncology Chief Development Officer, Dr. Johanna Bendell, echoed this sentiment, underscoring XTANDI’s unique position in the treatment landscape.
“As the only androgen receptor inhibitor demonstrating sustained five-year survival in this patient population, these data further reinforce XTANDI combined with androgen deprivation therapy as the standard-of-care for treating this advanced disease,” Bendell stated.
The five-year results from ARCHES will be submitted for peer-reviewed publication, ensuring broader dissemination among the oncology and urology communities.
Complementary Data from the ENZAMET Study Extends XTANDI’s Legacy to Eight Years
In addition to the five-year findings from ARCHES, the ASCO 2025 conference will also showcase new eight-year follow-up data from the ENZAMET trial, a Phase 3 study led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) and sponsored by the University of Sydney. The trial assessed XTANDI versus a non-steroidal anti-androgen (NSAA), both combined with testosterone suppression, with or without docetaxel, in men with mHSPC.
The ENZAMET results revealed that XTANDI extended median overall survival to 8.0 years compared to 5.8 years in the NSAA group (HR: 0.73; 95% CI: 0.63–0.86). At the 96-month mark, survival rates stood at 50% for the XTANDI arm and 40% for those receiving NSAA. Progression-free survival (PFS) also favored XTANDI, with a hazard ratio of 0.49 (95% CI: 0.42–0.57), underscoring its sustained disease control capabilities.
Dr. Christopher Sweeney, MBBS, of ANZUP and the ENZAMET study’s follow-up investigator, commented on the importance of these long-term data.
“These results further support the value of XTANDI as a treatment regimen for metastatic hormone-sensitive prostate cancer,” Dr. Sweeney said. “The data from the eight-year follow-up are highly encouraging, as they show the progression-free survival and overall survival benefits are sustained out to at least eight years.”
The trial also provided insight into the tolerability of long-term XTANDI therapy. The average duration of treatment was longer in the XTANDI group (58 months) compared to the NSAA group (36 months). Notably, 33% of patients in the XTANDI arm remained on treatment at eight years, with 88% of these still receiving the full 160 mg daily dose, reinforcing its long-term safety and usability.
XTANDI’s Global Reach and Milestone in Prostate Cancer Treatment
Since its initial regulatory approval in 2012, XTANDI has been approved in more than 90 countries, including the U.S., European Union, and Japan. More than one million patients worldwide have been treated with the drug, making it one of the most widely used androgen receptor pathway inhibitors in clinical practice.
As both the ARCHES and ENZAMET studies demonstrate sustained efficacy across a range of patient populations and treatment settings, XTANDI continues to reshape expectations for men diagnosed with mHSPC.
While the treatment landscape for prostate cancer has evolved dramatically over the past decade, the new data presented at ASCO solidify XTANDI’s position as a foundational therapy. As researchers, clinicians, and patients continue to seek therapies that not only prolong life but also preserve quality of life, XTANDI’s long-term data mark a critical milestone in addressing the complex challenges of advanced prostate cancer.
These developments also serve as a testament to the collaborative efforts of academic researchers, global cancer trial networks, and industry partners working to push the boundaries of cancer treatment and redefine what’s possible for patients facing metastatic disease. With survival outcomes that now extend as far as eight years for many men, XTANDI represents more than a pharmaceutical achievement—it’s a paradigm shift in prostate cancer care.
