Xtandi vs Zytiga: How do they compare?

• Castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

• Metastatic castration-resistant prostate cancer
• Metastatic high-risk castration-sensitive prostate cancer

• 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.

• 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).

• Fatigue
• Hypokalemia
• Hot flushes
• Edema
• Arthralgia
• Nausea
• Diarrhea
• Hypertension
• Vomiting
• Cough
• Headache
• Upper respiratory infection

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).

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).

• 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

• 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.