New results from two clinical trials looked at drug treatments that could benefit men with prostate cancer that has not yet spread, yet their disease is already resistant to hormone therapy. Men with this type of prostate cancer see their PSA levels rise, indicating that the cancer continues to grow; yet without evidence of metastasis (as shown on scans), they would not have access to drugs approved to target advanced metastatic prostate cancer. These patients generally have a poor prognosis. However, the new trials for apalutamide and enzalutamide could change this.
Apalutamide Reduces Risk of Metastatic Cancer,
Receives FDA Approval
Apalutamide (brand name Erleada) is an oral drug that blocks the effect of androgens, a group of hormones, on prostate tumors. These androgens, such as testosterone, can promote tumor growth.
In February, the U.S. Food and Drug Administration (FDA) approved apalutamide for the treatment of non- metastatic castration-resistant prostate cancer. This is the first FDA-approved treatment for this type of prostate cancer.
This FDA approval is also significant because it is the first time the agency has used metastasis-free survival as the endpoint to measure the effect of a drug. Metastasis-free survival measures the length of time during which the tumor did not spread to other parts of the body or that the patient died after starting treatment.
The FDA approval was based on phase 3 results from the SPARTAN trial, a randomized clinical trial of 1,207 men with non- metastatic castration-resistant prostate cancer. Patients in the study received either apalutamide or a placebo. The data showed that apalutamide decreased the relative risk of distant metastasis or death by 72% and delayed the spread of the disease by 2 years. Men in the apalutamide group had a median of 40.5 months of metastasis-free survival, compared to 16.2 months for patients in the placebo group.
All the men in the study also had hormone therapy, either with gonadotropin-releasing hormone (GnRH) analog therapy or surgical castration to lower the amount of testosterone in the body. The men had also undergone previous treatment for prostate cancer, either surgery or radiation therapy, yet their PSA scores doubled within 10 months or less even while they were on hormone therapy.
Phase 3 results from the study were presented at the American Society for Clinical Oncology Genitourinary Cancers (ASCO-GU) Symposium in February and received early release publication in the New England Journal of Medicine.
Enzalutamide Delays Time to Metastasis
Enzalutamide (brand name Xtandi) is drug that also blocks the androgen receptor. Previous studies have shown that enzalutamide significantly prolongs the survival of men with metastatic prostate cancer that is resistant to hormone therapy. The drug is already FDA-approved for this type of cancer.
However, new phase 3 results from the PROSPER trial indicate that the drug could also benefit men with non- metastatic prostate cancer that is hormone-resistant. The study found that men who received enzalutamide with androgen-deprivation therapy (ADT) lived longer before their cancer metastasized or they died. Enzalutamide led to a 71% reduction in the relative risk of developing metastatic castration-resistant prostate cancer. Similarly to apalutamide, enzalutamide delayed the time to metastasis by nearly 22 months. Men in the enzalutamide group had a median metastasis-free survival of 36.6 months, compared to 14.7 months for men in the placebo group.
The PROSPER trial included 1,401 men who were randomized to either received enzalutamide or a placebo. Men in the study also continued to have ADT.
The phase 3 results from the study were presented at the American Society for Clinical Oncology Genitourinary Cancers (ASCO-GU) Symposium in February. The manufacturers of Xtandi have requested approval from the FDA.