The IMAAGEN Study: Effect of Abiraterone Acetate and Prednisone on Prostate Specific Antigen and Radiographic Disease Progression in Patients with Nonmetastatic Castration Resistant Prostate Cancer

J Urol. 2018 Aug;200(2):344-352. doi: 10.1016/j.juro.2018.03.125. Epub 2018 Apr 6.

Abstract

Purpose: We evaluated the use of abiraterone acetate (1,000 mg) plus prednisone (5 mg) in patients with high risk, nonmetastatic, castration resistant prostate cancer.

Materials and methods: Patients considered at high risk for progression to metastatic disease (prostate specific antigen 10 ng/ml or greater, or prostate specific antigen doubling time 10 months or less) received abiraterone acetate plus prednisone daily in 28-day cycles. The primary study end point was the proportion of patients in whom a 50% or greater prostate specific antigen reduction was achieved during cycles 1 to 6. Secondary end points included time to prostate specific antigen progression, time to radiographic evidence of disease progression and safety.

Results: Of the 131 enrolled patients 44 (34%) remained on treatment with a median followup of 40.0 months. Median age was 72 years (range 48 to 90). Of the patients 82.4% were white and 14.5% were black. Median screening prostate specific antigen was 11.9 ng/dl and median prostate specific antigen doubling time was 3.4 months. Prostate specific antigen was significantly reduced (p <0.0001) with a 50% or greater prostate specific antigen reduction in 86.9% of cases and a 90% or greater reduction in 59.8%. Median time to prostate specific antigen progression was 28.7 months (95% CI 21.2-38.2). Median time to radiographic evidence of disease progression was not reached but on sensitivity analysis in 15 patients it was estimated to be 41.4 months (95% CI 27.6-not estimable). Baseline testosterone 12.5 ng/dl or greater and a 90% or greater prostate specific antigen reduction at cycle 3 were associated with longer time to prostate specific antigen progression and radiographic evidence of disease progression. Outcomes in black patients were similar to those in other patients. Adverse events, grade 3 or greater adverse events and serious adverse events were reported in 96.2%, 61.1% and 43.5% of patients, respectively.

Conclusions: In patients with high risk, nonmetastatic, castration resistant prostate cancer treatment with abiraterone acetate plus prednisone demonstrated a significant 50% or greater prostate specific antigen reduction with encouraging results for the secondary end points, including the safety of 5 mg prednisone.

Keywords: abiraterone acetate; adverse events; prednisone; prostate-specific antigen; prostatic neoplasms.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Abiraterone Acetate / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / diagnostic imaging*
  • Bone Neoplasms / secondary
  • Disease Progression
  • Disease-Free Survival
  • Drug Administration Schedule
  • Humans
  • Kallikreins / blood*
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prednisone / therapeutic use*
  • Prostate / diagnostic imaging
  • Prostate / pathology
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / diagnostic imaging
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / pathology

Substances

  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen
  • Abiraterone Acetate
  • Prednisone