The ENZAMET Study: Adding Enzalutamide to ADT in Metastatic Hormone-Sensitive Prostate Cancer Extends Survival
Another inspiring presentation at the 2019 ASCO meeting was an interim analysis of the international, randomized phase III ENZAMET trial.
The trial found that 80% of men with metastatic hormone-sensitiveprostate cancer who received enzalutamide (Xtandi) along with standard-of-care treatment (ADT) were alive after three years, compared with just 72% of men who received other nonsteroidal antiandrogens along with standard ADT therapy. These findings were presented 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, Ph.D., of Monash University Eastern Health Clinical School, Victoria, Australia.
The study found that enzalutamide is more effective than the current standard of care using bicalutamide, nilutamide, or flutamide, the comparison standard nonsteroidal antiandrogens used in the trial. However, enzalutamide can lead to different side effects.
The trial involved men with metastatic hormone-sensitive prostate cancer (yes, we said hormone sensitive) who 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 other 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.
Men were followed for a median of 34 months. After three years, 80% of men with metastatic hormone-sensitive prostate cancer who received enzalutamide along with ADT, with or without early docetaxel, were alive, compared with 72% of men who received one of the other three nonsteroidal antiandrogens.
Overall, there was a 33% decrease in the risk of death in men receiving enzalutamide compared to those who took another nonsteroidal antiandrogen.
On a sub-group analysis, 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
It should be 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.
THE BOTTOM LINE
Substituting Xtandi (enzalutamide) for the commonly used anti-androgen treatments (bicalutamide, nilutamide, or flutamide) along with ADT provides an increase in survival advantage in both low and high volume disease.