The phase III ENZAMET study showed 'practice-changing' results with enzalutamide for men with metastatic hormone-sensitive prostate cancer.
CHICAGO-Adding enzalutamide to the current standard of care may significantly improve overall survival (OS) in men with metastatic hormone-sensitive prostate cancer (HSPC), according to an interim analysis of the international randomized phase III ENZAMET study (abstract LBA2) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago. Researchers found that 80% of men with metastatic HSPC who received this nonsteroidal anti-androgen (NSAA) drug along with the standard-of-care treatment were alive after 3 years compared with 72% of men who received other NSAAs along with standard treatment.
The study, which was led by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, found that enzalutamide was a more effective inhibitor of the androgen receptor compared with bicalutamide, nilutamide, or flutamide, but it can lead to different side effects. Study co-chair Christopher Sweeney, MBBS, a medical oncologist at the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, said that enzalutamide represents a new treatment option for men who cannot tolerate chemotherapy. “The study is well-powered and will change practice. The most important take-home message is enzalutamide added to testosterone suppression increases overall survival in patients with high and low volume of disease,” Sweeney told Cancer Network.
In the trial, the results of which were published simultaneously in the New England Journal of Medicine, 1,125 men with metastatic HSPC were randomly assigned to receive an injection of a testosterone suppression agent (goserelin, leuprolide, or degarelix) with either a 160-mg enzalutamide pill daily or one of three standard NSAAs (bicalutamide, nilutamide, or flutamide). The men were treated between March 2014 and March 2017 and were followed for a median of 34 months. In this trial, 503 men received early doses of docetaxel and 602 did not. Overall, there was a 33% decrease in the risk of death in men receiving enzalutamide compared with those who received another NSAA.
When the researchers looked at outcomes for the 596 men with a higher amount of disease on imaging scans, they found that 71% taking enzalutamide were alive compared with 64% taking another NSAA. When they looked at the 529 men with a low amount of disease on imaging scans, they found that 90% taking enzalutamide were alive compared with 82% taking another NSAA.
The increase in survival with enzalutamide was most obvious in men who did not receive docetaxel. Among patients who received enzalutamide without docetaxel, 83% were alive compared with 70% taking another NSAA. The researchers also found that 64% of men were still taking enzalutamide compared with 36% of men taking another NSAA at the time of the first analysis of the data.
One important question that the trial sought to understand was how well enzalutamide was compared against docetaxel or combined with docetaxel. The researchers found that enzalutamide and docetaxel are both active and are reasonable alternatives, but have different side effects, costs, risks, and benefits.
Overall, side effects known to be associated with enzalutamide were observed and only a modest increase in adverse events were reported compared with men receiving one of the standard NSAAs. Serious adverse events were reported in 42% of men taking enzalutamide compared with 34% of the men taking one of the other NSAAs.
The researchers now plan to combine these findings with results from similar trials, so that they have a dataset that includes more than 10,000 men. Sweeney said that with such a large dataset, it will be possible to make extensive comparisons between agents and determine which might benefit specific groups of men the most.
Bobby Liaw, MD, medical director of the Blavatnik Family - Chelsea Medical Center at Mount Sinai in New York, said that these study findings are clinically relevant. He said having more treatment options gives clinicians and their patients more flexibility to tailor therapy. “We are starting to see our cadre of highly active therapeutic agents traditionally used in the arena of metastatic castration-resistant prostate cancer slowly migrating into the metastatic hormone-sensitive prostate cancer setting. Docetaxel and abiraterone have already been adopted for metastatic HSPC over the last 3 to 4 years, and this year we’re having all these new exciting data report out for both apalutamide (TITAN) and enzalutamide (ARCHES, ENZAMET), each proving their own activity and clinical benefits in metastatic HSPC,” he told Cancer Network.
Liaw also noted that there are some men who may not be the best candidates for chemotherapy or a treatment that requires steroids such as abiraterone, and so the addition of enzalutamide and apalutamide are certainly welcome. “But we still need to be quite mindful of potential side effects, risks, and costs associated with these drugs,” he said.