Efficacy
& Safety

STUDY DESIGN

Phase 3, randomized, double-blind, placebo-controlled, multicenter study (Study 1) in patients with mCRPC who received prior docetaxel therapy (N=1,195)

In this Phase 3 clinical study, patients were to continue until disease progression, initiation of new treatment, unacceptable toxicity or withdrawal.

All of the following criteria were to be met prior to discontinuation due to progression:1

  • Increased PSA* as defined by the PSA Working Group (PSAWG) (25% increase over baseline, with a minimum PSA increase of 5 ng/mL)
  • Radiographic progression (progression on bone scans or soft-tissue disease progression)
  • Symptomatic or clinical progression defined by pain progression, development of skeletal-related events, increase in prednisone or prednisolone dose, or change in corticosteroid to treat prostate cancer–related signs and symptoms

*PSA=prostate-specific antigen.


References: 1. Protocol for: de Bono JS, Logothetis CJ, Molina A, et al; for the COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995-2005. http://www.nejm.org/action/showSupplements?doi=10.1056%2FNEJMoa1014618&v....
Accessed March 29, 2016.

 

DURATION OF TREATMENT

At the updated analysis for overall survival, the median duration of treatment in patients with mCRPC who received prior docetaxel therapy was:1

ZYTIGA® + Prednisone
7.4 MONTHS

Placebo + Prednisone
3.6 MONTHS

PATIENT POPULATION

Patients were using a gonadotropin-releasing hormone analog or were previously treated with orchiectomy and had serum testosterone levels <50 ng/dL.

Select baseline patient demographics and disease characteristics:

  • Median age=69 years2
  • ECOG performance score of 0 to 1=89%
  • Brief Pain Inventory-Short Form score of ≥4 (patients reported worst pain over the previous 24 hours)=45%
  • Bone metastases=90%; visceral involvement=30%
    - The most common sites of visceral disease were the lungs (42%) and liver (33%). Other sites included prostate mass, bladder, and adrenal glands3
  • Prior cytotoxic chemotherapy: 1 regimen=70%; 2 regimens=30%
  • Radiographic evidence of disease progression=70%; PSA-only progression=30%

ECOG=Eastern Cooperative Oncology Group.
PSA=prostate-specific antigen.

Patients were using a gonadotropin-releasing hormone agonist or were previously treated with orchiectomy and had serum testosterone levels <50 ng/dL. Selected exclusion criteria included prior ketoconazole treatment for prostate cancer and a history of cardiovascular disease: LVEF<50% or New York Heart Association (NYHA) Class III or IV heart failure. Patients were not eligible if AST and/or ALT ≥2.5X ULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT >5X ULN. Concurrent use of spironolactone was not allowed during the study period.1


References: 1. de Bono JS, Logothetis CJ, Molina A, et al; for the COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995-2005.

Clinical Study Results

 

Median Overall Survival

The primary survival analysis showed a 3.9-month difference in median OS for ZYTIGA® + prednisone compared with placebo + prednisone* (14.8 months vs 10.9 months, respectively) (HR=0.646; 95% CI: 0.543, 0.768; P<0.0001).

4.6 MONTHS IMPROVEMENT IN MEDIAN OVERALL SURVIVAL OVERALL SURVIVAL (OS) AT THE UPDATED ANALYSIS

Median OS: 15.8 months with ZYTIGA® plus prednisone vs 11.2 months with placebo plus prednisone 1 (active compound)*

HR=0.740; 95% CI: 0.638, 0.859; P<0.0001.4

*Prednisone, as a single agent, is not approved for the treatment of prostate cancer.

 

Kaplan-Meier Survival Curve

Kaplan-Meier curves of patients treated with either ZYTIGA® + prednisone or placebo + prednisone (primary survival, intent-to-treat-analysis).

HR=0.646; 95% CI: 0.543, 0.768; P<0.0001

ADT rFPS Endpoint Curve

SAFETY PROFILE

Mineralocorticoid excess: Use ZYTIGA® with caution in patients with a history of cardiovascular disease. The safety of ZYTIGA® in patients with LVEF < 50% or NYHA Class III or IV heart failure in Study 1 or LVEF < 50% or NYHA Class II to IV heart failure in Study 2 was not established. Control hypertension and correct hypokalemia before treatment. Monitor blood pressure, serum potassium and symptoms of fluid retention at least monthly.

Adrenocortical insufficiency: Monitor for symptoms and signs of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations.

Hepatotoxicity: Can be severe and fatal. Monitor liver function and modify, interrupt, or discontinue ZYTIGA® dosing as recommended.

Please see full Important Safety Information below.

 

Adverse reactions in patients in the ZYTIGA® + prednisone arm in Study 1*

Adverse Reactions

ZYTIGA® + prednisone

(n=791)

Placebo + prednisone

(n=394)

Joint swelling/discomfort

29.5%

23.4%

Muscle discomfort

26.2%

23.1%

Edema§

26.7%

18.3%

Hot flush

19.0%

16.8%

Hypertension

8.5%

6.9%

Diarrhea

17.6%

13.5%

Dyspepsia

6.1%

3.3%

Urinary tract infection

11.5%

7.1%

Upper respiratory tract infection

5.4%

2.5%

Cough

10.6%

7.6%

Urinary frequency

7.2%

5.1%

Nocturia

6.2%

4.1%

FracturesII

5.9%

2.3%

Arrhythmia

7.2%

4.6%

Chest pain or chest discomfort#

3.8%

2.8%

Cardiac failure**

2.3%

1.0%

Adverse reactions

ZYTIGA® + prednisone

(n=791)

Placebo + prednisone

(n=394)

Joint swelling/discomfort

4.2%

4.1%

Muscle discomfort

3.0%

2.3%

Edema§

1.9%

0.8%

Hot flush

0.3%

0.3%

Hypertension

1.3%

0.3%

Diarrhea

0.6%

1.3%

Dyspepsia

0%

0%

Urinary tract infection

2.1%

0.5%

Upper respiratory tract infection

0%

0%

Cough

0%

0%

Urinary frequency

0.3%

0.3%

Nocturia

0%

0%

FracturesII

1.4%

0%

Arrhythmia

1.1%

1.0%

Chest pain or chest discomfort#

0.5%

0%

Cardiac failure**

1.9%

0.3%

References: 1. Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomized, double-blind, placebo-controlled Phase 3 study. Lancet Oncol. 2012;13(10):983-992. 2. de Bono JS, Logothetis CJ, Molina A, et al; for the COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995-2005. 3. Goodman OB, Flaig TW, Mulders PFA, et al. Exploratory analysis of the visceral disease subgroup in a Phase 3 study of abiraterone acetate in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2014;17:34-39. 4. Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomized, double-blind, placebo-controlled Phase 3 study. Lancet Oncol. 2012;13(10):983-992.