Impact of bone-targeted therapies in chemotherapy-naïve metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: post hoc analysis of study COU-AA-302

Eur Urol. 2015 Oct;68(4):570-7. doi: 10.1016/j.eururo.2015.04.032. Epub 2015 May 16.

Abstract

Background: Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy.

Objective: Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients.

Design, setting, and participants: This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial.

Intervention: Patients were grouped by concomitant BTT use or no BTT use.

Outcome measurements and statistical analysis: Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models.

Results and limitations: While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p=0.01) and increased the time to ECOG deterioration (HR 0.75; p<0.001) and time to opiate use for cancer-related pain (HR 0.80; p=0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients.

Conclusions: AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naïve mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT.

Patient summary: Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone in combination with bone-targeted therapy, there was a continued trend in prolongation of life when compared with patients treated with prednisone alone.

Trial registration: ClinicalTrials.gov NCT00887198.

Keywords: Abiraterone acetate; Bone-targeted therapy; Chemotherapy-naïve; Metastatic castration-resistant prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abiraterone Acetate / adverse effects
  • Abiraterone Acetate / therapeutic use*
  • Aged
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / etiology
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / secondary
  • Clinical Trials, Phase III as Topic
  • Disease-Free Survival
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Odds Ratio
  • Prednisone / therapeutic use
  • Proportional Hazards Models
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Risk Factors
  • Steroid Synthesis Inhibitors / adverse effects
  • Steroid Synthesis Inhibitors / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Bone Density Conservation Agents
  • Steroid Synthesis Inhibitors
  • Abiraterone Acetate
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT00887198