Cedars-Sinai Cancer investigators have identified two promising new treatment options for men with non-metastatic recurrent prostate cancer—enzalutamide (Astellas and Pfizer’s Xtandi) with androgen deprivation therapy (ADT), or enzalutamide alone. Each of these regimens beat the current standard treatment, which is ADT alone. The combination of ADT plus enzalutamide reduced the risk of metastasis or death by 58% over standard therapy, while enzalutamide alone reduced the risk of metastasis or death by 37% over ADT alone.
The companies released some promising results earlier this year. But full results of this international Phase III clinical trial were published this week in the New England Journal of Medicine.
Enzalutamine is an adrogen receptor antagonist already approved for several types of prostate cancer. It’s been on the market since 2019. But If these new approvals are granted, they will offer important new options for patients, since ADT has limitations and serious side effects, as well as new revenue for its makers.
“If these treatments are approved by the Food and Drug Administration, our results will be practice changing,” said Stephen Freedland, MD, the Warschaw, Robertson, Law Families Chair in Prostate Cancer at Cedars-Sinai, and lead author of the study. “In the study, both of these new options improved metastasis-free survival while preserving quality of life.”
About 288,300 men in the U.S. alone will be diagnosed with prostate cancer this year, according to American Cancer Society. Some of these men may never need treatment because they have a slow-growing form of the disease. Those with more aggressive prostate cancer are often first treated with surgery or radiation therapy.
“Unfortunately, in about a third of those patients, the cancer recurs within 10 years,” Freedland said.
Patients with aggressive recurrence usually receive ADT, which reduces testosterone production. Testosterone helps prostate cancer cells grow and spread, and ADT reduces these effects. But there are downsides to ADT.
“When you go on ADT, the testosterone level in the blood is reduced, but not completely eliminated,” Freedland said. “And the concern is that the testosterone that remains may still be enough to stimulate tumor growth. Also, patients don’t love the idea of being on hormones.”
In this study of 1,068 prostate cancer patients from 244 sites in 17 countries, Freedland and fellow investigators tested two experimental interventions—one to address each of these issues.
One-third of the trial patients received ADT plus enzalutamide, which blocks the effects of testosterone. Another third of the patients received enzalutamide alone. The final group of patients received ADT alone, which is the current standard treatment.
“We wanted to see whether enzalutamide on its own was so effective that we didn’t need the ADT,” Freedland said.
As noted, the team found that the combination of ADT plus enzalutamide reduced the risk of metastasis or death by 58% over ADT alone. They found that enzalutamide alone reduced the risk of metastasis or death by 37% over ADT alone. Both treatments maintained quality of life relative to the ADT alone.
“While the combination therapy offers greater risk reduction, some men might prefer enzalutamide alone. It does a good job of preventing cancer spread or death, with different side effects that may be more acceptable for some men,” Freedland said.
The next step is for the makers of enzalutamide to apply for FDA approval, so the new regimens can come into wide use, Freedland said.
“Optimizing therapy for patients with aggressive recurrence after their prostate cancer is initially treated has been an unmet need,” said Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer. “The results of this trial point the way to two options which the study showed were more effective than current standard of care.”
