Phase 3 ARCHES Trial Five-Year Follow-Up: Enzalutamide Plus ADT Reduces Risk of Death by 30% in Men with Metastatic Hormone-Sensitive Prostate Cancer

China Finance News Online, May 29th: Recently, Astellas Pharma, Inc. announced the long-term follow-up results of the open-label extension of the Phase 3 ARCHES (NCT02677896) study, reporting five-year overall survival (OS) data in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The results showed that treatment with Xtandi (enzalutamide) in combination with androgen deprivation therapy (ADT) reduced the risk of death by 30% compared to placebo plus ADT.

These data will be presented orally at the American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #5005).

"For a long time, the five-year survival rate of patients with mHSPC prostate cancer has been relatively low. However, with the advancement of initial intensified treatment regimens represented by Enzalutamide (Xtandi), such therapies are becoming the standard treatment," said Dr. Andrew J. Armstrong, Director of the Prostate and Urologic Cancer Center at the Duke Cancer Institute and principal investigator of ARCHES. "In our five-year follow-up of the global ARCHES study, two-thirds of male patients have now survived for five years. Compared to standard hormone therapy alone, the absolute five-year survival rate increased by 13%, with a relative survival improvement of 30%. Additionally, patients achieved significant clinical benefits regardless of whether they had a high or low tumor burden."

In patients with high tumor burden (HR: 0.70; 95% CI: 0.56-0.88), an improvement in median OS of 36 months was observed. Additionally, assessments were conducted in other clinically relevant subgroups, showing consistent survival benefits: low tumor burden (HR: 0.71; 95% CI: 0.49-1.05); patients previously treated with docetaxel (HR: 0.67; 95% CI: 0.43-1.05) and those not previously treated with docetaxel (HR: 0.71; 95% CI: 0.57-0.88). After five years of follow-up, the incidence of treatment-emergent adverse events was consistent with previous ARCHES analyses, and no new safety signals were identified.

"The survival benefits of Enzalutamide in the treatment of advanced prostate cancer have been widely recognized," added Shontelle Dodson, Executive Vice President of Medical Affairs and Head of Medical Affairs at Astellas. "The growing and accumulating body of research data on Enzalutamide further solidifies its long-term efficacy and patient benefits across all stages of prostate cancer, including metastatic stages, and demonstrates that Enzalutamide is transforming patients' life trajectories."

The five-year follow-up results of the ARCHES study will be submitted for publication in a peer-reviewed journal.

In addition to the five-year data from the ARCHES study, the eight-year data from the ENZAMET study, which evaluates enzalutamide versus non-steroidal anti-androgen (NSAA) (both in combination with testosterone suppression, with or without docetaxel) in the treatment outcomes of mHSPC, will also be presented during the ASCO poster session. This independent phase 3 trial, initiated by the University of Sydney (NCT02446405) and led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), demonstrated a reduction in the risk of death among men with mHSPC.

"The eight-year follow-up data for Xtandi (Enzalutamide) is very encouraging, showing that the benefits in progression-free survival and overall survival can last for at least eight years," said Dr. Christopher Sweeney from the ANZUP Cancer Trials Group in Sydney, Australia, and the principal investigator for the ENZAMET study follow-up. These results further confirm the value of Xtandi as a treatment option for metastatic hormone-sensitive prostate cancer.

In a study with a median follow-up time of 98 months, patients with mHSPC received either enzalutamide combined with testosterone suppression or NSAA combined with testosterone suppression. Each group had the option to use or not use docetaxel in combination. The results showed that the median OS was 8.0 years in the enzalutamide group and 5.8 years in the NSAA group (HR: 0.73; 95% CI: 0.63-0.86). The 8-year survival rate was 50% in the enzalutamide group and 40% in the NSAA group; progression-free survival (PFS) was better in the enzalutamide group than in the NSAA group (HR: 0.49; 95% CI: 0.42-0.57). Prostate cancer-related deaths accounted for 468 of all 622 deaths, with fewer prostate cancer deaths in the enzalutamide group than in the NSAA group (207 vs. 261). The total number of deaths from other causes was 154, with similar distribution frequencies between the enzalutamide group and the NSAA group (78 vs. 76). The average treatment duration of enzalutamide (58 months) was longer than that of NSAA (36 months), and 33% of patients were still receiving enzalutamide treatment, 88% of whom maintained the full dose of 160 mg.

Enzalutamide has been approved in more than 90 countries, including the United States, the European Union, and Japan. Since its initial approval in 2012, over one million patients worldwide have received treatment with Enzalutamide.