2019 ASCO: ENZAMET: Addition of Enzalutamide to Standard of Care in Metastatic Hormone-Sensitive Prostate Cancer
An interim analysis of the international, randomized phase III ENZAMET trial found that 80% of men with metastatic hormone-sensitive prostate cancer who received the nonsteroidal antiandrogen agent enzalutamide along with standard-of-care treatment were alive after 3 years, compared with 72% of men who received other nonsteroidal antiandrogens along with standard treatment. These findings were presented during the 2019 ASCO Annual Meeting Plenary Session by Sweeney et al (Abstract LBA2).
“Physicians and patients with prostate cancer now have a new treatment option with enzalutamide, and this is especially relevant for men who cannot tolerate chemotherapy and have a lower burden of disease seen on scans,” said study Co-Chair Christopher Sweeney, MBBS, a medical oncologist at the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston.
“In men with metastatic prostate cancer starting testosterone suppression, enzalutamide and docetaxel are both active and are reasonable alternatives, but they have different side effects, costs, risks, and benefits,” added study Co-Chair Ian D. Davis, PhD, of Monash University Eastern Health Clinical School, Victoria, Australia.
The study found that enzalutamide is a more effective inhibitor of the androgen receptor than bicalutamide, nilutamide, or flutamide, the comparison standard nonsteroidal antiandrogens used in the trial. However, enzalutamide can lead to different side effects.
Methods
Men with metastatic hormone-sensitive prostate cancer were randomly assigned between March 2014 and March 2017 to receive an injection of a testosterone-suppressing medicine (such as goserelin, leuprolide, or degarelix) with either a 160-mg dose of enzalutamide daily or one of three standard nonsteroidal antiandrogens: bicalutamide, nilutamide, or flutamide. Of the 1,125 men enrolled in the trial, 503 men received early doses of docetaxel, and 602 did not.
Results
Men were followed for a median of 34 months. After 3 years, 80% of men with metastatic hormone-sensitive prostate cancer who received enzalutamide along with testosterone suppression, with or without early docetaxel, were alive, compared with 72% of men who received one of the other three nonsteroidal antiandrogens in the trial. Overall, there was a 33% decrease in the risk of death in men receiving enzalutamide compared to those who took another nonsteroidal antiandrogen.
Of 596 men with a higher amount of disease on imaging scans, 71% taking enzalutamide were alive compared with 64% taking another nonsteroidal antiandrogen. Of 529 men with a low amount of disease on imaging scans, 90% taking enzalutamide were alive compared with 82% taking another nonsteroidal antiandrogen.
Among patients who received enzalutamide without docetaxel, 83% were alive, compared with 70% taking another nonsteroidal antiandrogen. At the time of the first analysis of the data, 64% of men were still taking enzalutamide, compared with 36% of men taking another nonsteroidal antiandrogen. Serious adverse events occurred in 42% of men taking enzalutamide compared with 34% of the men taking one of the other nonsteroidal antiandrogens.
Dr. Sweeney noted that a survival benefit is not seen with docetaxel in men with a low volume of disease, but that enzalutamide does improve survival in these men.
Next Steps
The results from this trial are being compiled with results from similar trials so that researchers have a data set that includes over 10,000 men. With that large data set at hand, researchers hope to be able to make extensive comparisons between medicines and determine which might benefit specific groups of men the most, according to Dr. Sweeney.
Disclosure: The study was led by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group. ENZAMET (ANZUP 1304) is a global collaborative investigator-initiated trial led by ANZUP Cancer Trials Group and sponsored by the University of Sydney, in collaboration with Canadian Cancer Trials Group, Dana-Farber Cancer Institute, and Cancer Trials Ireland (enrolling patients from Ireland and the United Kingdom). Astellas Pharma provided drug and financial support but was not involved in study conduct or data analysis. ANZUP receives infrastructure funding from the Australian Government through Cancer Australia. For full disclosures of the study authors, visit coi.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
