Treatment with ZYTIGA plus prednisone also resulted in an estimated 21 percent reduction in risk of death [HR=0.79; 95% CI: 0.66, 0.96, P=0.0151]. The median overall survival (OS) in the ZYTIGA arm was 35.3 months and was 30.1 months in the control arm. At the time of this interim analysis, conducted when approximately 55 percent of overall survival events (deaths) occurred, the pre-specified p-value for statistical significance was not met.
Secondary Endpoints Treatment with ZYTIGA plus prednisone also resulted in significant improvements in all secondary study endpoints compared to the control arm, specifically:
- 39 percent decrease in the risk of initiation of cytotoxic chemotherapy for prostate cancer: a median of 26.5 months for the ZYTIGA arm vs. 16.8 months for the control arm [HR=0.61 (95% CI: 0.51, 0.72); P<0.0001].
- 29 percent decrease in the risk of opiate use for cancer pain: the median time for the ZYTIGA arm was not reached and was 23.7 months for the control arm [HR=0.71; 95% CI: (0.59, 0.85); P<0.0002].
Safety FindingsNo new safety concerns were identified with the longer treatment with ZYTIGA compared to previously reported findings with the drug in mCRPC patients who had prior chemotherapy. In this interim analysis, fatigue, fluid retention, low blood potassium, hypertension, cardiac disorders and elevated liver transaminase enzymes were adverse events (AEs) reported more frequently in the ZYTIGA arm compared to the control arm. Patients in the ZYTIGA arm of the study experienced more grade 3 and grade 4 AEs than those in the control arm. Grade 3 or 4 AEs classified as liver toxicity, consisting primarily of reversible elevations in liver transaminase enzymes, were reported in more patients in the ZYTIGA arm than in the control arm.
Janssen previously announced that an Independent Data Monitoring Committee (IDMC) unanimously recommended unblinding this Phase 3 study after an earlier interim analysis found a statistically significant difference in rPFS and a trend in the difference in OS. Based on these results, the IDMC also recommended that patients in the control arm be offered treatment with abiraterone acetate.Study DesignStudy COU-AA-302 is a Phase 3, randomized, double-blind, multicenter, placebo-controlled international clinical study, which evaluated 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. Patients were randomized either to receive ZYTIGA 1,000 milligrams (mg) administered orally once daily plus prednisone 5 mg administered orally twice daily, or placebo orally daily plus prednisone 5 mg administered twice daily. The co-primary endpoints of the study are rPFS and OS.