Generic Name and Formulations:
Abiraterone acetate 250mg; tablets.
Company:
Janssen Biotech, Inc.
RECENT UPDATES
01/03/13
Removed docetaxel from indication. Updated warnings/precautions with mineralcorticoid excess, adrenocortical insufficiency, hepatotoxicity.
Indications for ZYTIGA:
In combination with prednisone for the treatment of metastatic castration-resistant prostate cancer.
Adult Dose for ZYTIGA:
Take on empty stomach (no food 2 hours before or 1 hour after administration). Swallow whole with water. 1g once daily (in combination with prednisone 5mg twice daily). Moderate hepatic impairment (Child-Pugh Class B): 250mg once daily. If hepatotoxicity occurs: interrupt, then restart at reduced dose; discontinue if severe (see literature).
Children's Dose for ZYTIGA:
Not recommended.
Pharmacological Class:
CYP17 inhibitor.
Contraindications:
Pregnancy (Cat. X). Women who are or may become pregnant.
Warnings/Precautions:
Risk of mineralocorticoid excess: patients with history of cardiovascular disease, LVEF <50%, Class III or IV heart failure, recent MI, ventricular arrhythmias. Monitor BP, serum potassium, and for fluid retention monthly. Control hypertension and correct hypokalemia before and during treatment. Monitor for adrenocortical insufficiency. Stress (may need higher corticosteroid dose). Baseline severe hepatic impairment (Child-Pugh Class C); avoid. Monitor liver function (ALT/AST, bilirubin) prior to starting treatment, every 2 weeks for the first 3 months, and monthly thereafter; interrupt, reduce dose, or discontinue if hepatic dysfunction occurs. Nursing mothers: not recommended.
Interactions:
CYP2D6 substrates with narrow therapeutic index (eg, thioridazine); avoid. Potentiates dextromethorphan. May affect, or be affected by, strong inhibitors or inducers of CYP3A4; avoid or use caution.
Adverse Reactions:
Joint swelling or discomfort, hypokalemia, edema, myalgia, hot flush, GI upset, UTI, cough, hypertension, arrhythmias, urinary frequency, nocturia, URI, adrenocortical insufficiency, hepatotoxicity.
Note:
Pregnant women and those of childbearing potential should not handle Zytiga tablets without protection (eg, gloves). Partners must use appropriate barrier contraception.
Metabolism:
Hepatic; >99% protein bound.
Elimination:
Fecal (primarily), renal.
Generic Availability:
NO
How Supplied:
Tabs—120
Zytiga Approved for Expanded Prostate Cancer Indication
ZYTIGA (abiraterone acetate) 250mg tablets by Centocor Ortho Biotech Janssen announced that the FDA has approved Zytiga (abiraterone acetate), in combination with prednisone, for the treatment continuum for metastatic castration-resistant prostate cancer (mCRPC) before the use of chemotherapy.
Prior to this approval, Zytiga with prednisone had been approved to treat men with mCRPC who had received prior chemotherapy containing docetaxel.
The new approval is based on a supplemental New Drug Application (sNDA) that included efficacy and safety results of a Phase 3, randomized, double-blind, placebo-controlled international clinical study, which eva luated Zytiga plus prednisone vs. placebo plus prednisone in men (n=1,088) with mCRPC who had failed androgen deprivation therapy and had not received cytotoxic chemotherapy.
Zytiga, a CYP17 inhibitor, was first approved by the FDA in 2011.
Zytiga Approved for Metastatic Prostate Cancer
ZYTIGA (abiraterone acetate) 250mg tablets by Centocor Ortho Biotech Centocor Ortho Biotech announced that the FDA has approved Zytiga (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel. This approval was based on results from a Phase 3, randomized, placebo-controlled, multicenter study that showed that at pre-specified interim analysis, treatment with Zytiga in combination with prednisone resulted in a 35% reduction in the risk of death (14.8 months vs. 10.9 months; hazard ratio (HR) = 0.646 [0.543–0.768]; P<0.0001) and a 3.9 month difference in median survival compared to placebo plus prednisone. In an updated analysis, results were consistent with those from the interim analysis with a 4.6 month difference between the two arms in median survival (15.8 months vs. 11.2 months [HR = 0.74]).
Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis.
Phase 3 Study Update for Zytiga Plus Prednisone in Metastatic Castration-Resistant Prostate Cancer
Janssen Research & Development announced further results from pre-specified interim analyses of the Phase 3 study of Zytiga (abiraterone acetate) plus prednisone for the treatment of asymptomatic or mildly symptomatic chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (CRPC). Results showed a statistically significant improvement in radiographic progression-free survival (rPFS) and a trend for increased median overall survival (OS), the co-primary endpoint, in patients receiving Zytiga plus prednisone.
The COU-AA-302 study was an international, randomized, double-blind, placebo controlled study that included 1,088 asymptomatic or mildly symptomatic patients with mCRPC who had not received chemotherapy. Data showed statistically significant improvement in rPFS in the Zytiga arm of the study compared to the control arm (n=150 vs. 251, respectively; HR=0.43; 95% confidence interval [0.35, 0.52]; P<0.0001). Additionally, treatment with Zytiga plus prednisone resulted in an estimated 33% improvement in survival (HR=0.75; 95% confidence interval: [0.61, 0.93], P=0.0097).
Zytiga in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.
Zytiga Plus Prednisone Phase 3 Study Update in Metastatic Castration-Resistant Prostate Cancer
Janssen Research & Development announced updated results from the Phase 3 study of Zytiga (abiraterone acetate) plus prednisone demonstrating that it continued to provide statistically significant improvements in disease progression compared to placebo plus prednisone, and longer overall survival in men with metastatic castration-resistant prostate cancer (mCRPC).
Study COU-AA-302 was a Phase 3, randomized, double-blind, multicenter, placebo-controlled international clinical study, which eva luated Zytiga plus prednisone compared to placebo plus prednisone in 1,088 men with mCRPC who had failed androgen deprivation therapy and had not received cytotoxic chemotherapy. The co-primary endpoints of the study are radiographic progression-free survival (rPFS) and overall survival (OS).
The analysis showed a statistically significant 47% reduction in risk of disease progression, which was measured as rPFS in the Zytiga plus prednisone arm compared to the placebo plus prednisone arm. The median rPFS was 16.5 months in the Zytiga arm vs. 8.3 months in the control arm [hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.45 to 0.62; P<0.0001]. At the time of the interim analysis, the co-primary endpoint of overall survival was not met.
Zytiga is approved in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).
Priority Review Granted for Zytiga for Metastatic Castration-Resistant Prostate Cancer Before Chemotherapy
Janssen Research & Development announced that the FDA has granted Priority Review to the supplemental New Drug Application (sNDA) for Zytiga (abiraterone acetate) administered in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy.
The Zytiga sNDA submission is based on the efficacy and safety results of an international Phase 3, randomized, double-blind, placebo-controlled clinical study that eva luated Zytiga plus prednisone compared to placebo plus prednisone in 1,088 asymptomatic or mildly symptomatic men with mCRPC who had not received chemotherapy.
Zytiga in combination with prednisone was approved by the FDA in April 2011 for the treatment of patients with mCRPC who have received prior chemotherapy containing docetaxel.
sNDA Submitted for Zytiga Plus Prednisone for Metastatic Castration Resistant Prostate Cancer
Janssen Research & Development submitted a supplemental New Drug Application (sNDA) to extend the use of Zytiga (abiraterone acetate) administered with prednisone for the treatment of patients with metastatic castration resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy and before chemotherapy.
The regulatory application follows the announcement of results observed from pre-specified interim analyses of the international Phase 3, randomized, double-blind, placebo-controlled COU-AA-302 clinical study. This study, which included 1,088 asymptomatic or mildly symptomatic men with mCRPC who had not received chemotherapy, eva luated the effect of Zytiga plus prednisone on the co-primary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) compared to placebo plus prednisone. The company previously announced the study was unblinded based on the unanimous recommendation of an Independent Data Monitoring Committee (IDMC). Based on these results, the IDMC also recommended that patients in the control arm be offered treatment with Zytiga.
Zytiga in combination with prednisone was approved by the FDA in April 2011 for the treatment of men with mCRPC who have received prior chemotherapy containing docetaxel.
Phase 3 Study Update of Zytiga Plus Prednisone for Chemotherapy-Naive Patients with Metastatic Castration-Resistant Prostate Cancer
Janssen Research & Development announced that it has unblinded the Phase 3 study of Zytiga (abiraterone acetate) plus prednisone for the treatment of asymptomatic or mildly symptomatic patients with metastatic castration-resistant prostate cancer (CRPC) who have not received chemotherapy.
Study COU-AA-302 was an international, randomized, double-blind, placebo controlled study that included 1,088 patients who were randomized to receive ZYTIGA 1,000mg administered once daily plus prednisone 5mg administered twice daily or placebo plus prednisone 5mg administered twice daily. The co-primary endpoints of the study were radiographic progression-free survival and overall survival.
The Independent Data Monitoring Committee (IDMC) unanimously recommended unblinding the study based on a planned interim analysis in which differences in radiographic progression-free survival, overall survival, and secondary endpoints were observed that constitute evidence of clinical benefit as well as continued evidence of favorable safety in patients receiving abiraterone acetate plus prednisone as compared to those receiving placebo plus prednisone. Based on these results, the IDMC also recommended that patients in the placebo arm be offered treatment with Zytiga.
Zytiga in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC) who have received prior chemotherapy containing docetaxel.
ASCO: Abiraterone Tolerated in High-Risk Prostate Cancer
ASCO: Abiraterone Tolerated in High-Risk Prostate Cancer (HealthDay News) – For men with localized high-risk prostate cancer, neoadjuvant androgen deprivation therapy with abiraterone acetate (AA) plus leuprolide acetate (LHRHa) is well tolerated and has good pathological complete/near complete response (pCR/near pCR) rates, according to a study released May 16 in advance of presentation at the annual meeting of the American Society of Clinical Oncology, held from June 1–5 in Chicago.
Mary-Ellen Taplin, MD, from Harvard Medical School and the Dana-Farber Cancer Institute in Boston, and colleagues conducted a randomized Phase 2 trial for neoadjuvant AA/LHRHa in 58 men (median age, 58 years) with localized high-risk prostate cancer. Participants were randomly allocated to receive LHRHa (28 men) or AA/LHRHa/prednisone (30 men) for 12 weeks. After 12 weeks, all men received AA/LHRHa/prednisone for a further 12 weeks, followed by radical prostatectomy.
The researchers found that the pCR/near pCR was 25% overall, and was 34% for those treated with AA for 24 weeks and 15 percent for those treated with AA for 12 weeks. Grade 3 elevated aspartate aminotransferase/alanine aminotransferase and hypokalemia were seen in 9% and 5% of patients, respectively, and no Grade 4 mineralocorticoid-related adverse events were observed.
"For this proportion of patients with high-risk disease to have very little to no detectable cancer in the prostate after six months of therapy is dramatic," Taplin said in a statement. "Our findings suggest that this combination therapy approach could improve outcomes for a substantial number of men, but larger, long-term trials are needed to confirm this approach."
Several authors disclosed financial ties to pharmaceutical companies, including Johnson & Johnson, which manufactures abiraterone acetate.
Abiraterone Prolongs Survival in Metastatic Prostate Cancer
Abiraterone Prolongs Survival in Metastatic Prostate Cancer (HealthDay News) – Abiraterone acetate significantly improves overall survival in patients with metastatic castration-resistant prostate cancer that has progressed after docetaxel treatment, according to a study published online Sept 18 in The Lancet Oncology.
Karim Fizazi, MD, from University of Paris-Sud in Villejuif, and colleagues enrolled 1,195 participants in an international, multicenter study in which patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel treatment were randomly assigned (ratio 2:1) to receive either abiraterone acetate (797 participants; 1,000mg, orally once daily) plus prednisone (5mg, orally twice daily) or placebo (398 participants) plus prednisone.
The researchers found that, at a median follow-up of 20.2 months, median overall survival was significantly longer for the abiraterone group than the placebo group (hazard ratio [HR], 0.74; 95% confidence interval, 0.64–0.86). For the abiraterone group vs. the placebo group, median time to prostate-specific antigen (PSA) progression (8.5 vs. 6.6 months; HR, 0.63), median radiologic progression-free survival (5.6 vs. 3.6 months; HR, 0.66), and proportion of patients who had a PSA response (29.5 vs. 5.5%) were all significantly improved. Fatigue, anemia, back pain, and bone pain were the most common grade 3–4 adverse events in both groups.
"This final analysis confirms that abiraterone acetate significantly prolongs overall survival in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel treatment," Fizazi and colleagues conclude.
Several authors disclosed financial ties to pharmaceutical companies, including Janssen Research & Development, which funded the study.
