Maui—In the IMAAGEN (Impact of Abiraterone Acetate in Prostate Specific Antigen) core study, patients with non-metastatic castration-resistant prostate cancer (MO-CRPC) had statistically significant reductions in prostate-specific antigen (PSA) levels at 6 months with a therapy regimen of abiraterone acetate (Zytiga®) plus prednisone (5 mg twice daily).
The primary end point was the proportion of patients with a ≥50% reduction in PSA during cycles 1 through 6. Secondary end points included testosterone levels, safety, time to PSA progression, and time to radiographic disease progression.
Abiraterone acetate is a selective, irreversible CYP17 inhibitor of androgen biosynthesis that significantly reduced testosterone production in the testes, adrenal glans, and prostate cancer tissue. In combination with 10 mg of prednisone daily, 1000 mg of abiraterone acetate is indicated for the treatment of patients with metastatic CRPC (mCRPC).
Patients with MO-CRPC will eventually progress to mCRPC. There is no current approved therapy for MO-CRPC. The IMAAGEN trial was designed to assess the ability of abiraterone acetate in combination with 5 mg of prednisone daily to decrease PSA levels in patients with MO-CRPC and rising PSA.
The phase 2, multi-center, open-label, single arm study in the United States included 131 patients with high risk MO-CRPC with PSA values ≥10 ng/mL or a PSA doubling time of ≤10 months at screening. Patients were enrolled from May 2011 to July 2013 at 38 sites in the United States.
Of the 131 patients enrolled, 14.5% were African American, 1.5% were Asian, and 82.4% were Caucasian. At baseline, median age was 72 years, median baseline PSA was 13.7 ng/mL (range 1.6-167.8 ng/mL). Study patients were given 1000 mg of abiraterone acetate plus 5 mg prednisone twice daily for the duration of the study. PSA assessment and imaging scans were conducted every 3 months.
Data from 122 of the 131 enrolled patients were available for evaluation for analysis of PSA response. By the end of 6 treatment cycles, 106 of the 122 patients (87%) had a ≥50% reduction in PSA and 73 (60%) had a ≥90% reduction. No patient required increasing the prednisone dose to >5 mg for management of mineralocorticoid excess symptoms.
In summary, the researchers said, “In men with high-risk MO-CRPC, treatment using [abiraterone acetate plus 5 mg prednisone] is very effective in lowering PSA. The rate and depth of PSA decline appear superior to men with mCRPC.”
Clinical trial information: NCT01314118