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Xtandi vs Zytiga: How do they compare?

Medically reviewed by Nicole France, BPharm. Last updated on Sep 21, 2021.

Official answer

by Drugs.com

Xtandi (enzalutamide) and Zytiga (abiraterone acetate) are both drugs that are used in the treatment of prostate cancer. Results from various analyses indicate that Xtandi is more effective than Zytiga in patients with castration-resistant prostate cancer that has spread or metastasized, although it’s more commonly associated with fatigue.

Xtandi (enzalutamide) Zytiga (abiraterone acetate)
Company Astella Pharma Janssen Biotech
Approval date First approved in the US in 2012 First approved in the US in 2011
Indication/usage For the treatment of:
  • Castration-resistant prostate cancer
  • Metastatic castration-sensitive prostate cancer
For the treatment of:
  • Metastatic castration-resistant prostate cancer
  • Metastatic high-risk castration-sensitive prostate cancer
Dosage form Capsules (40mg) and tablets (80mg, 40mg) Tablets (uncoated 250mg, film-coated 500mg)
Generic available Generic capsules only available Generics available
Administration Orally Orally
Dosing schedule
  • 160mg once daily + a gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy.

Capsules and tablets should be swallowed whole.

  • For metastatic castration-resistant prostate cancer 1000mg once daily + prednisone 5mg twice daily + a gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy.
  • For metastatic castration-sensitive prostate cancer 1000mg once daily + prednisone 5mg once daily + a gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy.

Tablets must be swallowed whole and taken on an empty stomach.

Drug type Small molecule Small molecule
Mechanism of action Androgen receptor inhibitor CYP17 inhibitor
Side effects / adverse effects The most common adverse reactions (≥ 10%) are:
  • Asthenia/fatigue
  • Back pain
  • Hot flushes
  • Constipation
  • Arthralgia
  • Decreased appetite
  • Diarrhea
  • Hypertension

Results from a systematic review and meta-analysis showed that Xtandi was associated with a significantly elevated risk of side effects (730 patients, odds ratio 0.35, 95% CI 0.13-0.92, p=0.03), especially fatigue (2477 patients, odds ratio 0.46, 95% CI 0.34-0.63, p<0.00001), compared with Zytiga in patients with metastatic castration-resistant prostate cancer.

However, a separate systematic review and meta-analysis comparing Xtandi with Zytiga in patients with metastatic castration-resistant prostate cancer did not find a significant difference between the two groups in terms of overall adverse events (730 patients, relative risk 0.42, 95% CI 0.14-1.31, p=0.14), but Xtandi was associated with a higher risk of fatigue (2555 patients, relative risk 0.45, 95% CI 0.24-0.85, p=0.01).

The most common adverse reactions (≥ 10%) are:
  • Fatigue
  • Hypokalemia
  • Hot flushes
  • Edema
  • Arthralgia
  • Nausea
  • Diarrhea
  • Hypertension
  • Vomiting
  • Cough
  • Headache
  • Upper respiratory infection
Efficacy Results from three systematic reviews and meta-analyses show that Xtandi is more effective than Ztygia for treating metastatic castration-resistant prostate cancer.

In two reviews prostate-specific antigen responses were higher for people receiving Xtandi than Zytiga (790 patients, odds ratio 0.47, 95% CI 0.29-0.77, p=0.003 and 867 patients, risk ratio 0.69, 95% CI 0.61-0.79, p<0.00001).

In a third review, Xtandi was more effective than Zytiga at improving radiographic progression-free survival (hazard ratio=0.516, 95% CI 0.438-0.608) and time to prostate-specific antigen progression (hazard ratio 0.365, 95% CI 0.303-0.441), but not overall survival (p=0.21), although more work was noted to be needed to confirm these findings.

Other studies have found Xtandi to be associated with an overall survival benefit compared with Zytiga in patients with metastatic castration-resistant prostate cancer, especially in older patients with more comorbidities who are not candidates for docetaxel (median overall survival 18.9 months vs 13.6 months, respectively (p<0.001).

Drug interactions
  • Avoid strong CYP3A4 inducers as they can decrease plasma exposure to Xtandi
  • Avoid strong CYP2C8 inhibitors as they can increase plasma exposure to Xtandi
  • Avoid CYP3A4, CYP2C9 (warfarin), CYP2C19 substrates with a narrow therapeutic index because Xtandi may decrease the plasma exposure of these drugs
  • Avoid strong CYP3A4 inducers. If they must be taken then then increase the Zytiga dosing frequency
  • Avoid CYP2D6 substrates that have a narrow therapeutic index. Exercise caution if one must be taken and consider a dose reduction of that drug
Warnings and precautions
  • Falls and fractures. Treat patients with bone-targeted agents according to guidelines.
  • Ischemic Heart Disease. Discontinue Xtandi for grade 3-4 events.
  • Seizures occurred in 5% of Xtandi-treated patients. Discontinue Xtandi if seizures develop.
  • Posterior reversible encephalopathy syndrome (PRES). Discontinue Xtandi.
  • Hypersensitivity. Discontinue Xtandi.
  • Increased fractures and mortality when used in combination with radium Ra 223 dichloride. Avoid using Zytiga in combination.
  • Mineralocorticoid excess.Monitor patients with cardiovascular disease, control hypertension and correct hypokalemia prior to treatment. Monitor blood pressure, potassium levels and signs of fluid retention at least monthly.
  • Adrenocortical insufficiency. Monitor for symptoms and adjust corticosteroid dose as required.
  • Hepatotoxicity, including severe and fatal cases. Monitor liver function and adjust treatment accordingly.
  • Embryo-fetal toxicity. Males should use effective contraception if their partner is able to get pregnant.
  • Hypoglycemia. Severe hypoglycemia possible in patients with diabetes taking thiazolidinediones or repaglinide. Monitor blood glucose levels and adjust diabetes medication as required.
Special patient populations Do not use in patients with existing severe hepatic impairment (Child-Pugh Class)

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