Adding Xtandi (enzalutamide) to androgen deprivation therapy (ADT) significantly delays disease progression or death in men with metastatic hormone-sensitive prostate cancer (mHSPC), regardless of how spread the disease is, a Phase 3 clinical trial shows.
It also improved several other patient outcomes, extending the time to a new cancer treatment and to worsening of pain, stretching the time to resistance to ADT, and reducing the likelihood of bone symptoms — all without added side effects or worsening quality of life.
The results were published in the Journal of Clinical Oncology in a paper titled, “ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer.”
ADT aims to reduce the amounts of active androgens, the so-called “male hormones” that can drive the growth of some prostate tumors. These cancers are thus referred to as “hormone-sensitive.”
Xtandi, developed by Pfizer and Astellas, works in a slightly different way, but toward the same end. The treatment blocks receptors for androgens, preventing them from sending signals to cancer cells.
Researchers questioned if these two therapies might control hormone-sensitive prostate cancers best if they are used together.
To find out, investigators conducted the ARCHES Phase 3 clinical trial (NCT02677896) at 202 centers in North and South America, Europe, and Asia. The trial enrolled 1,150 men with metastatic prostate cancer who were either just starting ADT or who had responded to prior ADT, with or without the chemotherapy docetaxel.
Participants were randomly assigned to treatment with either Xtandi or a placebo, both in combination with ADT. Most of the participants (62%) had “high volume” disease, which means that the cancer had already metastasized, or spread, to at least four sites in the body.
As of the data cutoff, 377 men — 65 on Xtandi, 171 on placebo — had discontinued study treatment, with disease progression as the primary reason. The median follow-up time was 14.4 months.
In the Xtandi group, there were 91 (15.9%) instances of disease progression or death, whereas in the placebo group, there were 201 (34.9%). Put another way, men on Xtandi were 61% less likely to experience disease progression or death than those on placebo. This association was independent of initial disease volume and prior docetaxel use.
Xtandi treatment also significantly reduced the likelihood of symptomatic skeletal events, including broken bones and fractures, compared with the placebo.
Likewise, during the study duration, patients on Xtandi were less likely to need a new cancer treatment or to experience an increase in their PSA levels — a validated biomarker of prostate cancer. The men on Xtandi also were more likely to respond to treatment.
As of the publication of the paper, overall survival was not significantly different between the two groups, but the data was premature. Put bluntly, not enough people have died for the researchers to know if there’s a statistical difference.
Rates of adverse events were similar between the two groups, and none of the adverse events recorded were unexpected. In all, 24 people died due to adverse events. However, the investigators determined that this was only treatment-related in one patient, who was on placebo plus ADT.
“This data, combined with that of the several additional recently reported studies, suggest that more potent androgen receptor inhibition leads to better outcomes for our patients with advanced prostate cancer,” Andrew Armstrong, MD, a professor at Duke University and co-author of the study, said in a press release.
Armstrong added that people with prostate cancer “now will have choices between several therapies, which is good news for our patients.”