TWO STUDIES. PROVEN EFFICACY. NEW INDICATION.
ZYTIGA® has been evaluated in 2 clinical trials and is approved for use in combination with prednisone in patients with mCRPC, and achieved differences in median overall survival. The following illustration is not intended to suggest ZYTIGA® is the only treatment option following ADT.
Overview of Clinical Trial
The efficacy and safety of ZYTIGA® + prednisone vs. placebo + prednisone for the treatment of patients with mCRPC who had received prior chemotherapy containing docetaxel were evaluated in a Phase 3, randomized, double-blind, placebo-controlled, multicenter clinical study.1
Reference:
1. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer.
N Engl J Med. 2011;364:(21):1995-2005.
Study Design
Primary endpoint:
- Overall survival
Criteria for Discontinuation of Treatment Due to Progression
In the Phase 3 clinical study, all of the following criteria were required for discontinuation of study:1
- Prostate Specific Antigen (PSA) progression as defined by PSA Working Group eligibility criteria (25% increase over baseline) with minimum PSA increase of 5 ng/mL
- Protocol-defined radiographic progression (on bone scans or soft-tissue disease progression)
- Symptomatic or clinical progression defined by pain progression, development of a skeletal-related event, or any increase in prednisone or prednisolone dose
Other reasons for discontinuation of study included initiation of new treatment, unacceptable toxicity, or withdrawal.
References:
1.Data on file. Janssen Biotech, Inc.
Patient Population
Patients with metastatic CRPC who had received prior chemotherapy containing docetaxel. Patients were using a gonadotropin-releasing hormone (GnRH) agonist or were previously treated with orchiectomy and were at castration levels of testosterone (serum testosterone ≤ 50 ng/dL).1
References:
1. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer.
N Engl J Med. 2011;364:(21):1995-2005.
Results of the Clinical Trial
ZYTIGA® provides significant benefit for patients with mCRPC post-chemotherapy
Overall Survival Benefit: Updated Analysis
ZYTIGA® plus prednisone achieved a statistically significant improvement in median overall survival for patients with mCRPC who have received prior chemotherapy containing docetaxel.
Median overall survival was 15.8 months for the ZYTIGA® plus prednisone arm vs 11.2 months for the placebo plus prednisone arm (HR=0.74; 95% CI:0.638,0.859; P<0.0001)
Pre-Specified Interim Analysis
- A 35% reduction in the risk of death was observed (14.8 months vs 10.9 months median overall survival, respectively [hazard ratio (HR) = 0.646; 95% confidence interval (CI): 0.543, 0.768; P<0.0001])
- 3.9-month difference in median overall survival compared with placebo + prednisone
Adverse Reactions -The most common adverse reactions (≥10%) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion.
The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia.
References:
1. Lancet Oncol 2012; 13: 983-92.
Overview of Clinical Trial
The efficacy and safety of ZYTIGA® + prednisone vs placebo + prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who had not received prior cytotoxic chemotherapy were evaluated in a Phase 3, randomized, double-blind, placebo-controlled, multicenter clinical study.1
References:
1. Ryan CJ, Smith MR, Molina A, et al. Interim Analysis (IA) Results of COU-AA-302, a Randomized, Phase 3 Study of Abiraterone Acetate (AA) in Chemotherapy-Naïve Patients (pts) With Metastatic Castration-Resistant Prostate Cancer (mCRPC). ASCO 2012; p7.
Study Design
Coprimary endpoints:
- Overall survival
- Radiographic progression-free survival (rPFS)
Criteria for Discontinuation of Treatment
Patients continued treatment until:
- Radiographic or clinical disease progression*
- Unacceptable toxicity or withdrawal
*Cytotoxic chemotherapy, radiation or surgical treatment for cancer, pain requiring chronic opioids, or ECOG (Eastern Cooperative Oncology Group) performance status decline to 3 or more.
Patient Population
Patients with metastatic castration-resistant prostate cancer (mCRPC) who had not received prior cytotoxic chemotherapy. Patients were using a GnRH agonist or were previously treated with orchiectomy.
Results of the Clinical Trial
Radiographic Progression-free Survival Benefit (rPFS)
ZYTIGA® plus prednisone increased median rPFS
INDICATION
ZYTIGA® (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).
Indication
ZYTIGA® (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).
Important Safety Information
Contraindications- ZYTIGA® (abiraterone acetate) is not indicated for use in women. ZYTIGA® can cause fetal harm (Pregnancy Category X) when administered to a pregnant woman and is contraindicated in women who are or may become pregnant.
Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess - Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in blood pressure, hypokalemia, or fluid retention. ZYTIGA® may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Safety has not been established in patients with LVEF <50% or New York Heart Association (NYHA) Class III or IV heart failure (in study 1) or NYHA Class II to IV heart failure (in study 2) because these patients were excluded from these randomized clinical trials. Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly.
Adrenocortical Insufficiency (AI) - AI was reported in patients receiving ZYTIGA® in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA®. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.
Hepatotoxicity- Monitor liver function and modify, withhold, or discontinue ZYTIGA® dosing as recommended (see Prescribing Information for more information). Measure serum transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] and bilirubin levels prior to starting treatment with ZYTIGA®, every two weeks for the first three months of treatment, and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA® treatment and closely monitor liver function.
Increased ZYTIGA® Exposures with Food - ZYTIGA® must be taken on an empty stomach. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken. 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.
Adverse Reactions - The most common adverse reactions (≥ 10%) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion.
The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia.
Drug Interactions - ZYTIGA® is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Avoid co-administration with CYP2D6 substrates that have a narrow therapeutic index. If an alternative cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate. In vitro, ZYTIGA® inhibits CYP2C8. There are no clinical data on its use with drugs that are substrates of CYP2C8. Patients should be monitored closely for signs of toxicity related to the CYP2C8 substrate if used concomitantly with abiraterone acetate.
Based on in vitro data, ZYTIGA® is a substrate of CYP3A4. The effects of strong CYP3A4 inhibitors or inducers on the pharmacokinetics of abiraterone have not been evaluated, in vivo. Strong inhibitors and inducers of CYP3A4 should be avoided or used with caution during treatment with ZYTIGA®.
Use in Specific Populations - Do not use ZYTIGA® in patients with baseline severe hepatic impairment (Child-Pugh Class C).
