What is Zytiga (abiraterone)?

Zytiga (Abiraterone Acetate): A Key Treatment for Prostate Cancer

Zytiga (abiraterone acetate) is an oral medication that inhibits androgen biosynthesis by blocking CYP17 enzyme, effectively reducing testosterone production in the body to treat metastatic prostate cancer. It is administered with prednisone and has demonstrated significant survival benefits in both castration-resistant and castration-sensitive prostate cancer patients 1, 2.

Mechanism of Action

• Abiraterone acetate is converted in vivo to abiraterone, which inhibits 17α-hydroxylase/C17,20-lyase (CYP17), an enzyme required for androgen biosynthesis in testicular, adrenal, and prostatic tumor tissues 2
• By blocking CYP17, abiraterone prevents the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives, thereby inhibiting the formation of dehydroepiandrosterone (DHEA) and androstenedione, which are precursors of testosterone 2
• This mechanism allows for more complete androgen suppression than traditional androgen deprivation therapy (ADT) alone, as it targets non-testicular sources of androgens 1

FDA-Approved Indications

• Treatment of metastatic castration-resistant prostate cancer (mCRPC) in combination with prednisone 2, 1
• Treatment of metastatic castration-sensitive prostate cancer (mCSPC) in combination with prednisone 1
• Available in 250 mg uncoated tablets and 500 mg film-coated tablets 2

Clinical Benefits

In Metastatic Castration-Sensitive Prostate Cancer:

• Significantly improves overall survival when added to ADT (HR, 0.63; 95% CI, 0.5–0.76; P<.0001) 1
• Delays development of castration resistance (from median 14.8 to 33.2 months) 1
• Delays PSA progression (from 7.4 to 33.2 months) 1
• Recommended as a category 1 treatment option with ADT for newly diagnosed M1 castration-sensitive prostate cancer 1

In Metastatic Castration-Resistant Prostate Cancer:

• Prolongs overall survival in patients previously treated with docetaxel (14.8 months vs. 10.9 months with placebo) 3
• Improves radiographic progression-free survival in chemotherapy-naïve patients (16.5 months vs. 8.3 months with placebo) 3
• Considered a standard treatment option for symptomatic mCRPC patients with good performance status 1

Dosing and Administration

• Standard dose: 1,000 mg once daily on an empty stomach (at least one hour before or two hours after a meal) 2
• Alternative dosing: 250 mg once daily with a low-fat breakfast (may reduce financial toxicity and improve compliance) 1
• Must be co-administered with prednisone or prednisolone 5 mg once daily 2, 1
• Continue treatment until disease progression 1
• Dose adjustments required for patients with moderate hepatic impairment (Child-Pugh Class B): reduce to 250 mg once daily 2
• Contraindicated in patients with severe hepatic impairment (Child-Pugh Class C) 2

Common Side Effects and Monitoring

• Mineralocorticoid-related effects: hypertension, hypokalemia, fluid retention/edema 1, 3
• Hepatotoxicity: monitor liver function tests regularly 1
• Cardiac disorders: monitor for heart failure, arrhythmias 1, 2
• Fatigue and hot flushes 1
• Older patients (≥70 years) may experience increased toxicity 1

Important Considerations

• Blood pressure, renal function, and hepatic function should be monitored regularly during treatment 1
• Patients should continue ADT with an LHRH agonist or antagonist during abiraterone treatment to maintain castrate testosterone levels 1
• The medication should be taken exactly as prescribed, and patients should not stop taking it without consulting their healthcare provider 2
• Women who are pregnant or may become pregnant should not handle abiraterone tablets if broken, crushed, or damaged without protection (e.g., gloves) 2

Place in Therapy

• First-line option for metastatic castration-resistant prostate cancer 4
• Category 1 recommendation for metastatic castration-sensitive prostate cancer in combination with ADT 1
• Can be used before or after docetaxel chemotherapy depending on the clinical scenario 1
• Part of the treatment intensification strategy for metastatic castration-sensitive prostate cancer, which is strongly recommended over ADT monotherapy 1

Zytiga represents a significant advancement in prostate cancer treatment by targeting androgen biosynthesis more completely than traditional ADT, providing meaningful survival benefits across multiple disease states.