Enzalutamide improves the survival of men with prostate cancer sensitive to metastatic hormones

Enzalutamide, an oral androgen receptor inhibitor, may improve outcomes in men with metastatic hormone-sensitive prostate cancer (mHSPC), according to a large study presented by Christopher Sweeney, MBBS of the Lank Genitourinary Cancer Center of the Dana-Farber Research Institute Annual Congress of the Society of Clinical Oncology (ASCO).

An interim badysis of the randomized ANZUP-led International Phase III ENZAMET trial found that in men with mHSPC who received testosterone suppression, those who also received enzalutamide generally survived longer than those who also received nonsteroidal inhibitors of standard androgen receptors. Of the participants in the trial, 80% of people treated with enzalutamide were alive after three years, compared to 72% of men who received conventional inhibitors.

"These results are truly informative about the practice and add an effective drug option in the treatment of mHSPC," said study co-chair Sweeney, who presented the findings during the plenary session of the 39; ASCO. The plenary session presents four studies considered to have the greatest potential impact on patient care, on more than 6,000 abstracts presented at the 5-day conference. The details were published simultaneously in the New England Journal of Medicine.

"The addition of enzalutamide to the suppression of testosterone in men with mHSPC can enable much more effective cancer control and much longer survival," Sweeney said. "This is true both for patients with a high burden of disease, with multiple bone metastases or liver metastases, as well as for men with a lower burden of disease.The new treatment option is particularly relevant for men who do not tolerate chemotherapy and have a lower burden of the disease. "

"The benefits of enzalutamide had already been established for prostate cancers that no longer respond to hormone therapy," said Ian D. Davis, MBBS, Ph.D., president of ANZUP and co-chair of the study. "The actual outcome in patients who started hormone therapy, noting that patients had a 60% improvement in the time required to re-detect cancer and a 33% increased chance of survival, was much higher than expected."

The trial sought to understand how well enzalutamide was compared to docetaxel, a chemotherapy drug approved for the treatment of this disease, combined with docetaxel, and administered to approximately 45% of trial participants. ENZAMET has shown that in this population, "enzalutamide and docetaxel are both active and constitute a reasonable alternative, but have different side effects, costs, risks and benefits," said Sweeney.

Initial badyzes suggest that enzalutamide may offer more benefit than docetaxel in men with reduced metastatic burden due to suppression of testosterone, Sweeney said. However, he warned that this discovery should be investigated further. The combination of testosterone suppression with enzalutamide and docetaxel delayed the progression of the disease, but researchers must follow the trial participants to see if this triplet combination also improves the quality of life and overall survival.

Overall, at ENZAMET, adverse effects badociated with enzalutamide were observed and resulted in a modest increase in adverse events compared with men receiving one of the standard nonsteroidal antiandrogens.

The National Cancer Institute estimates that 175,000 men will be diagnosed with prostate cancer and 32,000 will die of it in the United States this year. Localized disease is diagnosed in approximately 95% of men via screening for prostate specific antigen (PSA). Most are cured by surgery or radiotherapy, and some do not need treatment, Sweeney said.

The remaining 5% of patients initially present a very aggressive disease, and many other patients re-offend after treatment for localized disease, but tend to have a slower progression of the disease. The US Food and Drug Administration has approved enzalutamide for men whose disease continues to progress, both for men treated with docetaxel and others. Other hormonal treatments have also been approved.

ENZAMET is a collaborative study initiated by researchers and led by the Australian and New Zealand Prostate Cancer Trial Group (ANZUP) and sponsored by the University of Sydney, in collaboration with the Canadian group D & D. Cancer Trials, Dana-Farber and Cancer Trials Ireland. Around the world, 83 research institutions participated. The trial recruited 1,125 participants and followed them for a median of 34 months. Astellas Pharma provided pharmaceutical and financial support to ENZAMET, but did not participate in the conduct or badysis of the study. Cancer Australia and the Canadian Cancer Society also contributed to the funding.