Xtandi vs Zytiga: How do they compare?

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
• Non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis

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

Brand only

Generic may be available, but different generics or brands may have different indications and doses.

Administration

Orally

Orally

Dosing schedule

• 160mg once daily
• Capsules and tablets should be swallowed whole.
• Dose may be modified due to adverse reactions or drug interactions

• Zytiga 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:

• Fatigue (tiredness) or feeling weak
• Swelling of extremities (edema)
• Back pain
• Joint pain
• Muscle pain, weakness, and stiffness
• Hot flushes
• Diarrhea
• Headache
• Upper respiratory tract infection

In the AFFRIM clinical trial (NCT00974311)

The most common adverse reactions (≥ 10%) are:

• Tiredness (fatigue)
• Low blood potassium levels (hypokalemia)
• Hot flushes
• Edema
• Joint pain (arthralgia)
• Nausea
• Diarrhea
• High blood pressure (hypertension)
• Vomiting
• Cough
• Headache
• Upper respiratory infection

In the pooled data from 5 randomized controlled trials

Efficacy

Results from a systematic review showed that Xtandi is more effective than Zytiga for treating metastatic castration-resistant prostate cancer:

• the time to prostate-specific antigen progression and
• radiographic progression-free survival.

Xtandi and Zytigo were not significantly different in overall survival.

Drug interactions

• Strong CYP3A4 Inducers
• Strong CYP2C8 Inhibitors
• Certain CYP3A4, CYP2C9, or CYP2C19 Substrates

• CYP3A4 Inducers
• CYP2D6 Substrates

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 0.6% of Xtandi-treated patients. Discontinue Xtandi if seizures develop.
• Posterior reversible encephalopathy syndrome (PRES). Discontinue Xtandi.
• Hypersensitivity. Discontinue Xtandi.
• Severe Dysphagia or Choking Related to Product Size: Consider using smaller Xtandi tablet(s) in patients who have difficulty swallowing. Discontinue XTANDI for patients who cannot swallow capsules or tablets.
• Embryo-Fetal Toxicity: XTANDI can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception.

• 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)