In a recent randomized clinical trial, the PRESIDE Trial, Enzalutamide (Xtandi) showed that chemotherapy with docetaxel (Docetaxel) not only improved survival in men with metastatic castration-resistant prostate cancer (mCRPC), it sometimes reversed enzalutamide resistance.
PRESIDE was a randomized clinical trial that treated 687 men with mCRPC across 123 European sites. All the men were administered enzalutamide in addition to hormone therapy (ADT). After 13 weeks, 271 men had an increase in their PSA and/or an increase in tumor size based on scans. At this point, they were randomly assigned to have either:
A. Triplet therapy, combining enzalutamide, docetaxel, and ADT, or
B. Docetaxel, ADT, and placebo.
The men receiving the triplet therapy outperformed those receiving only docetaxel plus ADT in progression-free survival. This finding indicates that the enzalutamide was still efficacious for those who were also receiving ADT and docetaxel. The difference was modest but statistically significant.
Both experimental groups had similar treatment-related side effects, primarily caused by the chemotherapy, docetaxel. However, the triplet group experienced more significant incidents (49% vs 39%).
A similar randomized trial (ABIDO) used abiraterone along with ADT and chemotherapy as an alternate triplet therapy. Data showed that this triplet had considerably worse toxicity, particularly causing neutropenia, the presence of abnormally few white blood cells in the blood leading to an increased susceptibility to infection.
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PRESIDE is the first evidence that docetaxel might reduce enzalutamide resistance when given together. It also suggests that triplet therapy may be helpful in men who have already developed castration resistance.
