Xtandi (enzalutamide), an androgen receptor inhibitor, significantly delays disease progression — as assessed through radiological imaging — or death in metastatic hormone-sensitive prostate cancer (mHSPC) patients, a Phase 3 clinical trial shows.

The benefits were seen independently of patients’ initial PSA levels, suggesting that, contrary to prior beliefs, PSA levels are not an accurate predictive factor of responses to Xtandi in these patients.

These findings were presented at the American Urological Association’s 2019 Annual Meeting, held May 3–6 in Chicago, in a poster titled, “Efficacy of Androgen Deprivation Therapy with Enzalutamide or Placebo in Metastatic Hormone-Sensitive Prostate Cancer: Prostate-Specific Antigen Results.”

Xtandi, developed by Pfizer and Astellas, is an approved treatment for men whose prostate cancer no longer responds to medical or surgical treatment that lowers testosterone, a condition called castration-resistant prostate cancer.

Aiming to determine if the therapy also could be used in men with metastatic disease who responded to their last testosterone-lowering treatment, researchers designed the multinational ARCHES Phase 3 trial (NCT02677896). It included a total of 1,150 mHSPC patients from the U.S., Canada, Europe, South America, and Asia-Pacific region.

Participants were assigned randomly to Xtandi or placebo, both given in combination with androgen deprivation therapy (ADT), except if they had had a bilateral orchiectomy (surgery to remove the testicles).

The trial’s main goal was radiographic progression-free survival — defined as the time patients lived without evidence of radiographic disease progression, or death, within 24 weeks of discontinuing treatment.

In a prior presentation, researchers had reported that ARCHES met its primary goal, with Xtandi lowering the risk radiographic progression or death by 61% compared to placebo, with a similar proportion of patients experiencing severe adverse side effects.

Now, researchers examined PSA-related effectiveness measures, including radiographic progression-free survival classified by initial PSA levels, time to PSA progression (a pre-specified rise in PSA levels), time to hormone treatment resistance, the rate of patients achieving undetectable PSA levels, and how much PSA had dropped from initial levels.

After a median follow-up of 14.4 months, researchers confirmed their initial findings that Xtandi lowers the risk of radiographic disease progression or death. But they also found that these benefits were seen regardless of a patient’s PSA level at beginning of treatment.

The treatment also reduced the risk of PSA progression by 81% and the chance of resistance to hormone treatment by 72%, compared to ADT alone.

Also, more patients on Xtandi saw their PSA levels drop by more than half  (92.9% versus 56.8% for those taking placebo), by more than 90% (72.8% versus 30%), or reach undetectable levels (68.1% versus 17.6%).

In general, a similar proportion of patients in both groups experienced severe adverse effects, with those in ARCHES being similar to the ones seen in other Xtandi trials.

Overall, these results support the long-term effectiveness of Xtandi at delaying disease progression or death in mHSPC patients, and suggest that initial PSA levels are not predictive of  responses to Xtandi, at least for patients who have received prior treatment with ADT.