From the Guidelines
Enzalutamide plus ADT significantly prolongs overall survival in men with castrate-sensitive metastatic prostate cancer compared to ADT alone, with a hazard ratio for death of approximately 0.67, representing a 33% reduction in the risk of death.
Key Findings
- The survival benefit of enzalutamide plus ADT is consistent across different disease volumes and regardless of prior docetaxel use, as demonstrated in the ENZAMET trial 1.
- Enzalutamide is typically administered at a dose of 160 mg orally once daily alongside continued ADT (typically a GnRH agonist or antagonist).
- Common side effects include fatigue, hot flashes, hypertension, and falls, with seizures being a rare but serious potential adverse effect 1.
Mechanism of Action
- The survival benefit is attributed to enzalutamide's mechanism as a potent androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway, providing more complete androgen blockade than ADT alone 1.
Clinical Implications
- Enzalutamide plus ADT should be offered to men with metastatic noncastrate prostate cancer, including those with de novo metastatic disease and those who have received prior local therapies, such as RP or RT for localized disease 1.
- Discussions with patients should include the lack of data regarding long-term benefits and the cost of enzalutamide treatment compared with other second-generation antiandrogens, such as abiraterone 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Overall Survival Benefit
- The addition of enzalutamide to androgen deprivation therapy (ADT) has been shown to prolong overall survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC) compared to ADT alone 2, 3, 4.
- In the ARCHES trial, enzalutamide plus ADT reduced the risk of death by 34% compared to placebo plus ADT, with a median overall survival not reached in either group (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P < .001) 3.
- The ENZAMET trial also demonstrated a significant improvement in overall survival with enzalutamide plus ADT compared to standard care, with a hazard ratio of 0.67 (95% CI, 0.52 to 0.86; P = 0.002) 2.
- A plain language summary of the ARCHES and ENZAMET follow-up studies confirmed that enzalutamide plus ADT improves overall survival in patients with mHSPC, with similar benefits seen in different patient groups 4.
Comparison of Studies
- The ARCHES trial compared enzalutamide plus ADT to placebo plus ADT, while the ENZAMET trial compared enzalutamide plus ADT to standard care (which may have included docetaxel) 2, 3.
- Despite these differences, both trials demonstrated a significant overall survival benefit with enzalutamide plus ADT compared to the control group.
- The results of these trials are consistent with each other and support the use of enzalutamide plus ADT as a treatment option for patients with mHSPC 2, 3, 4.