General Information

Xtandi (enzalutamide) is an androgen receptor inhibitor.

Xtandi is specifically indicated for the treatment of:

• castration-resistant prostate cancer (CRPC)
• metastatic castration-sensitive prostate cancer (mCSPC)
• non-metastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)

Dosing/Administration

Xtandi is supplied as a capsule for oral administration. 

The recommended dosage of Xtandi is 160 mg administered orally once daily with or without food until disease progression or unacceptable toxicity.

Swallow capsules or tablets whole. Do not chew, dissolve, or open the capsules. 

Patients with CRPC or mCSPC receiving Xtandi should also receive a gonadotropic-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

Patients with nmCSPC with high-risk BCR may be treated with Xtandi with or without a GnRH analog. For patients who receive Xtandi with or without a GnRH analog, treatment can be suspended if PSA is undetectable (< 0.2 ng/mL) after 36 weeks of therapy. Reinitiate treatment when PSA has increased to ≥ 2.0 ng/mL for patients who had prior radical prostatectomy or ≥ 5.0 ng/mL for patients who had prior primary radiation therapy.

Mechanism of Action

Xtandi (enzalutamide) is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors and inhibit androgen receptor nuclear translocation and interaction with DNA.

Side Effects

Adverse events associated with the use of Xtandi may include, but are not limited to, the following:

• Asthenia/fatigue
• Back pain
• Diarrhea
• Arthralgia
• Hot flush
• Peripheral edema
• Musculoskeletal pain
• Headache
• Upper respiratory infection
• Muscular weakness
• Dizziness
• Insomnia
• Lower respiratory infection
• Spinal cord compression and cauda equina syndrome
• Hematuria
• Paresthesia
• Anxiety
• Hypertension

Clinical Trial Results

The FDA approval of Xtandi was based on a randomized, placebo-controlled, multicenter trial in 1,199 subjects. The subjects were randomized to receive either Xtandi orally at a dose of 160 mg once daily (n=800) or placebo orally once daily (n=399). All subjects continued androgen deprivation therapy. The primary end point was overall survival. The prespecified interim analysis at the time of 520 events showed a statistically significant improvement in overall survival in subjects on the Xtandi arm compared to those on the placebo arm. The number of deaths was 308 (38.5 percent) in the Xtandi arm versus 212 (53.1 percent) in the placebo arm. The median survival was 18.4 months in the Xtandi arm versus 13.6 months in the placebo arm (p< 0.0001).

The FDA approval of Xtandi for nmCSPC with high-risk BCR was based on results from the Phase 3 EMBARK trial, which evaluated Xtandi plus leuprolide, placebo plus leuprolide, and Xtandi (single agent) in patients with nonmetastatic hormone- (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC) with high-risk BCR. Xtandi reduced risk of metastasis or death by 58% over hormone therapy leuprolide alone. Patients treated with Xtandi combined with leuprolide showed an 87% metastasis-free survival rate at five years. Xtandi as a monotherapy had an 80% metastasis-free survival rate while the leuprolide only arm came in at 71%.