Add-on Xtandi Prolongs Survival in Metastatic Hormone-sensitive PC, Trial Shows

Treatment with Xtandi (enzalutamide) and testosterone suppression prolonged the survival of men with metastatic hormone-sensitive prostate cancer in comparison with standard of care, according to early findings of a large Phase 3 trial.

The study, “Overall survival (OS) results of a phase III randomized trial of standard-of-care therapy with or without enzalutamide for metastatic hormone-sensitive prostate cancer (mHSPC): ENZAMET (ANZUP 1304), an ANZUP-led international cooperative group trial,” was presented at the recent American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

At the same time, the findings, “Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer,” were also published in the New England Journal of Medicine. 

Xtandi, marketed by Pfizer and Astellas Pharma, is an oral androgen receptor approved to treat prostate cancer that no longer responds to medical or surgical treatment intended to lower testosterone.

To address whether Xtandi also works in prostate cancers that are responding to testosterone-lowering treatments, researchers designed the multi-center, global and investigator-initiated ENZAMET trial (NCT02446405).

The study is being led by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, partially funded by Astellas Pharma, and supported by The University of Sydney, the Canadian Cancer Trials Group, Dana-Farber Cancer Institute, and Cancer Trials Ireland.

It included 1,125 patients, followed over a median 34 months, who received Xtandi or standard androgen receptor inhibitors in addition to testosterone suppression, with or without docetaxel.

Early results showed that 80% of the men treated with testosterone suppression and Xtandi were alive after three years, compared to 72% of those on standard androgen receptor inhibitors. The group given Xtandi also had longer progression-free survival (PFS) — the period patients are alive and without disease worsening — as determined by PSA levels, imaging, symptoms, signs, or changes in therapy.

“Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression,” the scientists stated.

“These findings are truly practice-informing, adding an effective drug option in treating mHSPC,” Christopher Sweeney, the study presenter and co-chair from Dana-Farber, said in a press release.

“Adding enzalutamide to testosterone suppression in men with mHSPC can give much better cancer control and much longer survival,” Sweeney said. Although also true in patients with high burden of disease, Sweeney noted that “the new treatment option is especially relevant for men who cannot tolerate chemotherapy and have a lower burden of disease.”

In patients starting on hormonal therapy, treatment with Xtandi led to a 61% improvement in the time until detection of cancer growth and a 33% greater likelihood of survival. Ian D. Davis, PhD, ANZUP chair and the study’s co-chair, noted that these benefits were “far higher than we expected.”

The findings also suggested that among men with a lower burden of metastatic disease and given testosterone suppression, Xtandi may outperform the chemotherapy docetaxel. In turn, combining testosterone suppression with both Xtandi and docetaxel improved PFS. Potential effects on quality of life and overall survival will be analyzed at a later time.

Overall, the trial suggests that Xtandi and docetaxel “are both active and are reasonable alternatives but have different side effects, costs, risks, and benefits,” Sweeney said.

Regarding safety, the patients taking Xtandi had a modest increase in the frequency of adverse events, such as fatigue and seizures. Serious adverse events within 30 days of treatment were found in 42% of patients given Xtandi and 34% of those on standard therapy. Treatment discontinuation due to adverse events was more common in patients on Xtandi than in the standard-care group (33 events versus 14 events).

Of note, Sweeney has received consulting fees from Astellas and Pharma; both he and Davis work at institutions that have received research funding and consulted for the two companies.