Xtandi

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Xtandi

Enzalutamide

FDA approved oral medication for castration resistant prostate cancer.  

Manufactured by Medivation and Astellas Pharma Inc.

www.Xtandihcp.com, www.astellas.com, www.medivation.com

 

Xtandi was initially Approved in 2012 for use after chemotherapy men with metastatic castration resistant prostate cancer. This was based on the AFFIRM trial which demonstrated the following: (https://www.xtandihcp.com/mcrpc-results/primary-endpoints-affirm-trial)

Results Xtandi plus ADT versus ADT alone after chemotherapy.

  • 37% reduction in risk of death
  • 18.4 months versus 13.6 months.  Improved by 4.8 months.
  • Improvement in secondary endpoints including the following:
    • >50% decline in PSA (54% vs. 2%)
    • radiographic response (29% vs. 4%)
    • radiographic progression-free survival (8.3 vs. 2.9 months)
    • time to first SRE (16.7 vs. 13.3 months).
  • Quality of life measured was improved with enzalutamide compared to placebo.
  • Discontinuations due to adverse events 16% Xtandi versus 18% placebo treated patients.

 

Subsequently the use of Xtandi was expanded based on the PREVAIL trial in pre-chemotherapy patients with castration resistant metastatic prostate cancer. (https://www.xtandihcp.com/mcrpc-results/primary-endpoints-prevail-trial)

Results Xtandi plus ADT versus ADT alone

  • Reduced the risk of radiographic progression or death by 83%
  • Overall survival 35.3 months versus 31.3 months.
  • 23%-29% reduction in the risk of death
  • Delayed time to initiation of chemotherapy and time to skeletal related event (SRE)
  • Delayed median time to initiate chemotherapy by 17 months.

 

Recently the use of Xtandi has been expanded once again for treatment of patients in nonmetastatic, castration resistant prostate cancer.  The new indication was based on the PROSPER TRIAL (www.xtandihcpcom/nmcrpc-results)

 

Indications:

  • PSA>(greater than or equal) 2 ng/ml
  • At least 2 consecutive rises
  • Castrate testosterone levels </= 50 ng/dl

Results Xtandi plus ADT versus ADT alone

  • 36.6 month metastasis free survival adding Xtandi to ADT versus 14.7 months ADT alone
  • 71% reduction in the risks of metastasis or death.
  • 23% reduction in risk of death
  • 83% reduction in risk of radiographic progression or death

 

How does Xtandi work?

Xtandi is a oral “androgen receptor inhibitor”. Xtandi blocks the binding of androgen to the androgen receptor.  CRPC growth usually requires androgen binding to the androgen receptor, followed by nuclear translocation, and then DNA binding to make sure the tumor received the signal it needs.

Xtandi causes 3 different things to make it effective:

  • 1)It blocks the ability of the androgen receptor to be translocated into the cell. This blocks the signal to the cancer cell.
  • 2)It blocks DNA binding, so a signal, even if it gets through, cannot be translated to or used by the cancer cells.
  • 3)Unlike a traditional anti-androgen drug,it does not have agonist activity.

 

Xtandi blocks the androgen receptor so well that other signals, hormones or compounds can not interact with the androgen receptor to stimulate growth.  Tumors not only stop growing but also shrink in many instances.

Dosage

160 mg (4 40 mg tabs) once daily with water. With or without food. Capsules should be swallowed whole and not chewed, dissolved or opened.

Advantages

  • Can be taken with or without food.
  • Serious side effects were equivalent in treatment and placebo groups.

Adverse effects

(https://www.xtandihcp.com/safety-adverse-reactions/prevail-trial)

A complete listing of adverse effects compared to placebo is available at the link above.

The most common side effects along with the most serious side effects are outlined below:

  • Fatigue is common and occurs in 47% of men.
  • Seizures occurred in 0.4% of men on Xtandi.  
    • Those with predisposing factors had a 2.2% incidence of seizure.
      • Predisposing factors include Traumatic brain injury, stroke or TIA, Alzheimer’s disease, meningioma, leptomeningeal disease and unexplained loss of consciousness in the last 12 months, history of seizure, space occupying brain lesion, history of arteriovenous malformation or history of brain infection.
    • Stop Xtandi in patients who develop a seizure during treatment.
  • Posterior reversible encephalopathy syndrome (PRES) is rare as it can cause rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness along with additional visual or neurological disturbances with or without high blood pressure. Condition confirmed by MRI and enzalutamide would be discontinued in patients who develop PRES.

The other most common adverse effects reported included back pain, decreased appetite, constipation, diarrhea, joint or muscle pain, hot flush, upper respiratory infections, swelling, weight loss, headache, dizziness and hypertension.

Safety information and drug interactions can be reviewed at the manufacturers website. (https://www.xtandihcp.com/safety-profile)

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