XTANDI (Enzalutamide) for Prostate Cancer: Indications and Use
Yes, XTANDI (enzalutamide) 40 mg capsule is indicated for the treatment of prostate cancer across multiple disease states, including castration-resistant prostate cancer, metastatic castration-sensitive prostate cancer, and non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis. 1
FDA-Approved Indications
Enzalutamide (XTANDI) is specifically indicated for:
- Castration-resistant prostate cancer (CRPC) - both metastatic and non-metastatic
- Metastatic castration-sensitive prostate cancer (mCSPC)
- Non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis 1
Dosing and Administration
- The recommended dose is 160 mg (four 40 mg capsules) administered orally once daily
- Can be taken with or without food
- Patients should swallow each capsule whole with sufficient water
- For patients with CRPC or mCSPC, concurrent GnRH analog therapy should be continued, or patients should have had bilateral orchiectomy 1
Clinical Evidence Supporting Use
Non-Metastatic CRPC
The PROSPER trial demonstrated that enzalutamide significantly improved:
- Metastasis-free survival: 36.6 months with enzalutamide vs. 14.7 months with placebo (HR=0.29; P<0.001)
- Overall survival: 67.0 months with enzalutamide vs. 56.3 months with placebo (HR=0.73; P=0.001)
- Time to PSA progression: 37.2 months vs. 3.9 months (HR=0.07; P<0.001) 2, 3
Metastatic CRPC
Enzalutamide has demonstrated efficacy in both pre-chemotherapy and post-chemotherapy settings:
- In patients with metastatic CRPC who had not received chemotherapy, enzalutamide significantly reduced the risk of radiographic progression and death compared to placebo
- Median radiographic progression-free survival was significantly longer with enzalutamide 4
Castration-Sensitive Prostate Cancer
The ARCHES and ENZAMET trials showed that enzalutamide plus ADT:
- Significantly reduced the risk of radiographic progression or death compared to ADT alone
- Demonstrated consistent benefits across subgroups including high-volume and low-volume disease 5
Guideline Recommendations
The American Urological Association (AUA) guideline states that enzalutamide is a novel AR signaling inhibitor that:
- Competitively inhibits androgen binding
- Inhibits nuclear translocation of the AR, DNA binding, and coactivator recruitment
- Binds AR with 5-8 fold higher affinity than bicalutamide 5
The American Society of Clinical Oncology (ASCO) strongly recommends enzalutamide for metastatic non-castrate prostate cancer:
- "ADT plus enzalutamide should be offered to men with metastatic noncastrate prostate cancer including both those with de novo metastatic disease and those who have received prior therapies, such as RP or RT for localized disease." 5
- The recommended regimen is enzalutamide 160 mg per day with ADT 5
Safety Considerations
Common adverse events (≥10% and ≥2% over placebo) include:
- Musculoskeletal pain
- Fatigue
- Hot flush
- Constipation
- Decreased appetite
- Diarrhea
- Hypertension
- Hemorrhage
- Falls and fractures
- Headache 1
Special warnings include:
- Seizure risk: Occurred in 0.6% of patients (2.2% in those with predisposing factors)
- Posterior reversible encephalopathy syndrome (PRES)
- Ischemic heart disease: Requires optimization of cardiovascular risk factors
- Falls and fractures: Evaluate patients for fracture and fall risk
- Severe dysphagia or choking: Consider using smaller tablets in patients with difficulty swallowing 1
Drug Interactions
- Strong CYP2C8 inhibitors: Avoid; if unavoidable, reduce enzalutamide dose
- Strong CYP3A4 inducers: Avoid; if unavoidable, increase enzalutamide dose
- Avoid coadministration with certain CYP3A4, CYP2C9, or CYP2C19 substrates 1
Enzalutamide has demonstrated significant improvements in overall survival, metastasis-free survival, and quality of life across multiple prostate cancer disease states, making it an important treatment option for patients with prostate cancer.