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Cancer Drug Information

  • Updated: 07/01/2013

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FDA Approval for Abiraterone Acetate

Brand name: Zytiga®

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

Approved for use with prednisone for metastatic castration-resistant prostate cancer before chemotherapy

On December 10, 2012, the Food and Drug Administration (FDA) approved an expanded indication for abiraterone acetate (Zytiga® tablets, made by Janssen Biotech, Inc.) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer.

The approval was based on a trial that randomly assigned patients with metastatic castration-resistant prostate cancer who had not received cytotoxic chemotherapy to either abiraterone acetate plus prednisone (N = 546) or placebo plus prednisone (N = 542). Entry was restricted to patients with metastases to the bone, soft tissue, or lymph nodes. Patients with moderate to severe cancer pain or opiate use for cancer pain were excluded. All patients had a prior orchiectomy or continued to receive a gonadotropin releasing hormone analog.

The co-primary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS). Treatment with abiraterone acetate improved rPFS. The median rPFS was 8.3 months for patients treated with placebo and had not yet been reached for those treated with abiraterone acetate [HR 0.43 (95 percent CI: 0.35, 0.52), p < 0.0001]. At the pre-specified third interim analysis, median OS was 35.3 months for patients treated with abiraterone acetate and 30.1 months for patients treated with placebo. [HR 0.79 (95 percent CI: 0.66, 0.96)]. These results did not cross the O’Brien-Fleming boundary for statistical significance. The primary endpoints were supported by statistically significant improvements in time-to-opiate use and time-to-cytotoxic chemotherapy.

Safety data were evaluated in 1333 patients with metastatic castration-resistant prostate cancer who received abiraterone acetate plus prednisone and in 934 patients who received placebo plus prednisone in this and the other pivotal trial. The most common (at least 10 percent) adverse reactions included fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and contusion. The most common laboratory abnormalities (more than  20 percent) included anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated aspartate aminotransferase (AST), hypophosphatemia, elevated alanine aminotransferase (ALT),  and hypokalemia.

Grade 3-4 adverse reactions occurred in 55 percent of patients who received abiraterone acetate and in 50 percent of those who received placebo. Grade 3-4 increases in ALT or AST occurred in 4 percent of patients treated with abiraterone acetate. Grade 3-4 cardiac failure occurred more commonly in patients treated with abiraterone acetate compared with those receiving placebo (1.6 percent vs. 0.2 percent). Adrenal insufficiency occurred in 0.5 percent of patients taking abiraterone acetate and in 0.2 percent of those receiving placebo. Patients should be monitored for adrenocortical insufficiency and mineralocorticoid excess.

The recommended dose and schedule for abiraterone acetate is 1000 mg administered orally once daily in combination with prednisone 5 mg administered orally twice daily.  Abiraterone acetate must be taken on an empty stomach. No food should be consumed for at least 2 hours before and at least 1 hour after abiraterone acetate. 

Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state

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Approved for use with prednisone for metastatic castration-resistant prostate cancer following docetaxel

On April 28, 2011, the FDA approved abiraterone acetate (ZytigaTM Tablets, made by Centocor Ortho Biotech, Inc.) for use in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have received prior chemotherapy containing docetaxel.

The approval is based on the results of a randomized placebo-controlled multicenter trial in 1195 patients with mCRPC previously treated with docetaxel-containing regimens. Patients were randomly assigned (2:1) to receive either abiraterone acetate orally at a dose of 1000 mg once daily (n = 797) or placebo once daily (n = 398). All patients received prednisone 5 mg orally twice daily. Treatment continued until disease progression (defined as a 25 percent increase in PSA over the patient’s baseline/nadir together with protocol-defined radiographic progression and symptomatic or clinical progression), unacceptable toxicity, initiation of new treatment, or withdrawal. Patients with prior ketoconazole treatment for prostate cancer and a history of adrenal gland or pituitary disorders were excluded.

A pre-specified interim overall survival (OS) analysis was performed when 552 events had occurred. This analysis demonstrated a statistically significant improvement in OS in patients receiving abiraterone acetate compared with patients who received the placebo. (HR = 0.646; 95 percent CI: 0.543, 0.768; p 0.0001). The median OS was 14.8 months for patients who received abiraterone acetate compared with 10.9 months OS for patients who received the placebo. An updated OS analysis, conducted after 775 events, demonstrated a median OS of 15.8 months for patients who received abiraterone acetate compared with 11.2 months for patients who received the placebo (HR = 0.740; 95 percent CI: 0.638, 0.859).

The most common adverse reactions (more than 5 percent of patients) were joint swelling or discomfort, hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia, and upper respiratory tract infection. The most common adverse drug reactions resulting in drug discontinuation were increased aspartate aminotransferase and/or alanine aminotransferase, urosepsis, and cardiac failure (each in less than 1 percent of patients taking abiraterone acetate).

The most common electrolyte imbalances in patients receiving abiraterone were hypokalemia (28 percent) and hypophosphatemia (24 percent). Following interruption of daily corticosteroids and/or with concurrent infection or stress, adrenocortical insufficiency ( less than 1 percent) has been reported in clinical trials in patients receiving abiraterone acetate at the recommended dose in combination with prednisone.

The recommended dose and schedule for abiraterone acetate is 1000 mg orally once daily in combination with prednisone 5 mg orally twice daily. Abiraterone acetate should be taken on an empty stomach. No food should be consumed for at least 2 hours before the dose of abiraterone acetate is taken and for at least one hour after the abiraterone acetate dose. 

This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

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