Trial: Improved Survival for Patients with Metastatic Prostate Cancer

The trial aimed to evaluate the survival rate of patients with metastatic hormone-sensitive prostate cancer who were treated with the combination of enzalutamide and androgen deprivation therapy.

Affecting approximately 38,000 men annually in the United States, metastatic hormone-sensitive prostate cancer (mHSPC) is a deadly form of cancer. Hormone, or castration, sensitivity refers to the fact that the disease still responds to medical or surgical treatment to lower testosterone levels.

The combination of enzalutamide (Xtandi, Astellas Pharma and Pfizer), an androgen receptor inhibitor, and androgen deprivation therapy (ADT) has found to improve radiographic progression-free survival in men with mHSPC.

Held at sites in the United States, Canada, Europe, South America and the Asia-Pacific region, the Phase 3 ARCHES trial was a randomized, double-blind, placebo-controlled, and international study that enrolled 1150 mHSPC patients. Patients were randomized to either receive a daily dose of 160-mg enzalutamide or placebo, and continued on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy, according to the press release.

The trial included both low- and high-volume disease and both newly diagnosed patients with mHSPC and patients who had prior definitive therapy and subsequently developed metastatic disease. The trial also included some patients who had received recent treatment with docetaxel for mHSPC, but whose disease had not progressed.

The trial demonstrated a 61% increase in radiographic progression-free survival (rPFS) through the combination of enzalutamide and standard hormonal therapy versus ADT alone; it also delayed disease progression. There were significant improvements in rPFS for all pre-specified subgroups, including disease volume, pattern of disease localization at baseline, geographic region, and prior docetaxel use. Adverse events (AEs) in the ARCHES clinical trial were generally consistent with those reported in enzalutamide clinical trials in patients with castration-resistant prostate cancer (CRPC).

“The ARCHES trial demonstrated that enzalutamide plus standard hormonal therapy delayed disease progression, and if approved, has the potential to be an important treatment option for men with prostate cancer that has spread but has not yet become hormone resistant,” said Andrew Armstrong, MD, professor of Medicine, Surgery, Pharmacology and Cancer Biology, and director of Research in the Duke Cancer Institute’s Center for Prostate and Urologic Cancers, in a prepared statement.

The findings from this trial have sparked discussion with the manufacturers and global health authorities on a new indication of enzalutamide, which is currently approved in the US and Japan for CRPC and EU for metastatic and high risk non-metastatic CRPC.