Why is prednisone (steroid) given with abiraterone (Zytiga)?

From the Guidelines

Prednisone is given with abiraterone to abrogate signs of mineralocorticoid excess that can result from treatment, including hypertension, hypokalemia, and peripheral edema 1.

Key Points

• The combination of abiraterone and prednisone is used to treat metastatic castration-resistant prostate cancer (CRPC) and metastatic castration-naïve prostate cancer.
• Prednisone is given at a dose of 5 mg twice daily to mitigate the mineralocorticoid excess effects of abiraterone.
• Monitoring of liver function, potassium and phosphate levels, and blood pressure readings is warranted during abiraterone therapy.
• Abiraterone can be given at 250 mg/day administered after a low-fat breakfast as an alternative to the dose of 1,000 mg/day after an overnight fast.
• The most common adverse reactions with abiraterone/prednisone include fatigue, back or joint discomfort, peripheral edema, diarrhea, nausea, and constipation.

Rationale

The use of prednisone with abiraterone is based on the results of several clinical trials, including the COU-AA-301 and COU-AA-302 trials, which demonstrated improved survival and delayed radiographic progression with the combination of abiraterone and prednisone compared to prednisone alone 1.

Clinical Implications

The combination of abiraterone and prednisone is a category 1, preferred option for mCRPC without prior novel hormone therapy, and is included in the “other recommended regimens” category for patients with mCRPC and prior novel hormone therapy 1.

• The fine-particle formulation of abiraterone can be used instead of the original formulation of abiraterone in the treatment of men with metastatic CRPC, but switching from one formulation to the other on disease progression should not be undertaken 1.
• Abiraterone with either steroid should not be given following progression on abiraterone with the other steroid.
• Symptom-directed assessment for cardiac disease is also warranted, particularly in patients with pre-existing cardiovascular disease.

From the FDA Drug Label

Advise patients to adhere to corticosteroids and to report symptoms of hypertension, hypokalemia, or edema to their healthcare provider [see Warnings and Precautions (5. 1)] . Adrenocortical Insufficiency Inform patients that abiraterone acetate with prednisone is associated with adrenal insufficiency.

• Prednisone is given with abiraterone to prevent adrenal insufficiency and minimize the risk of hypokalemia, hypertension, and fluid retention associated with abiraterone treatment 2, 2.
• The corticosteroid (prednisone) helps to mitigate these potential side effects by suppressing the body's natural cortisol production, which can be affected by abiraterone 2.

From the Research

Rationale for Co-administration of Prednisone with Abiraterone

• Abiraterone use for prostate cancer can cause mineralocorticoid excess syndrome (MES), which includes hypertension and hypokalemia 3.
• Prednisone mitigates these effects by reducing the mineralocorticoid excess caused by abiraterone 3, 4.
• The co-administration of prednisone with abiraterone is effective in reducing the risk of MES, with a study showing a statistically significant decrease in cumulative hazard for experiencing at least one MES event (hypertension and/or hypokalemia) with 5 mg of prednisone twice daily 3.
• The optimal dose of prednisone to mitigate MES while minimizing adverse effects is still being studied, with some research suggesting that 5 mg daily may be inadequate for some patients and 10 mg daily may cause adverse effects 4.

Clinical Benefits of Abiraterone plus Prednisone

• The combination of abiraterone and prednisone has been shown to significantly increase overall survival and radiographic progression-free survival in men with newly diagnosed, metastatic, castration-sensitive prostate cancer 5.
• Abiraterone acetate, in combination with prednisone, has also been approved for the treatment of men with metastatic castration-resistant prostate cancer (CRPC), with significant prolongation in overall survival and radiographic progression-free survival observed in clinical trials 6.
• The overall tolerability profile of abiraterone acetate, in combination with prednisone, is acceptable in men with metastatic CRPC, although it is associated with hypokalaemia, hypertension, and fluid retention or oedema, secondary to its mechanism of action 6.