Adding the androgen receptor inhibitor Xtandi (enzalutamide) to androgen deprivation therapy (ADT) significantly delays disease progression — assessed through radiological imaging — or death among metastatic hormone-sensitive prostate cancer patients, results of a Phase 3 trial show.
The benefits were seen across multiple patient subgroups, regardless of initial tumor volume, pattern of disease location, geographic region, and prior use of Taxotere (docetaxel), researchers said.
Xtandi, developed by Pfizer and Astellas, is an approved treatment for men whose prostate cancer no longer responds to medical or surgical treatment — a condition called castration-resistant prostate cancer.
While beneficial for castration-resistant prostate cancer patients, it remains unclear whether Xtandi also improves the outcomes of men whose tumors still respond to hormone therapy (hormone-sensitive prostate cancer). This has been the goal of two other Phase 3 trials — ARCHES, for metastatic patients, and EMBARK (NCT02319837) for those whose disease has not yet spread beyond the prostate.
The multinational ARCHES trial included 1,150 patients across the U.S., Canada, Europe, South America, and the Asia-Pacific region, who were randomly assigned Xtandi or a placebo.
ARCHES participants could be either newly diagnosed with metastatic disease or have received prior therapy and subsequently developed metastasis. They all continued to receive hormone therapy, unless they had had a bilateral orchiectomy (surgery to remove both testicles).
The trial’s main goal was radiographic progression-free survival — or the time to first evidence of radiographic disease progression, or death within 24 weeks of treatment discontinuation.
Secondary measures included overall survival, time to a skeletal event — bone disease, radiation to the bone, or spinal cord compression — time to PSA progression, time to a new anti-cancer treatment, and objective response rate.
Researchers now reported that the primary goal of ARCHES was met, with Xtandi reducing the risk of radiographic progression or death by 61%. The treatment also reduced the risk of PSA progression by 81% and the chance of starting a new anti-cancer treatment by 72%, compared to ADT alone.
However, the time to deterioration of urinary symptoms was similar between the two groups.
In general, adverse events in ARCHES were similar to those seen in trials of Xtandi for castration-resistant prostate cancer patients. While a similar proportion of patients in both groups experienced severe adverse events, Xtandi-treated patients more commonly reported hot flashes, fatigue, joint pain, high blood pressure, nausea, muscle pain, diarrhea, lack of energy, and dizziness.
Pfizer and Astellas are now planning to discuss the findings with regulatory authorities worldwide, and to pursue Xtandi’s approval for men with metastatic hormone-sensitive prostate cancer.
“The ARCHES trial demonstrated that Xtandi 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,” Andrew Armstrong, MD, professor of medicine, surgery, pharmacology and cancer biology, and director of research at the Duke Cancer Institute’s Center for Prostate and Urologic Cancers, said in a press release.