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.
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Date
2015-10-01ICR Author
Author
Saad, F
Shore, N
Van Poppel, H
Rathkopf, DE
Smith, MR
de Bono, JS
Logothetis, CJ
de Souza, P
Fizazi, K
Mulders, PFA
Mainwaring, P
Hainsworth, JD
Beer, TM
North, S
Fradet, Y
Griffin, TA
De Porre, P
Londhe, A
Kheoh, T
Small, EJ
Scher, HI
Molina, A
Ryan, CJ
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Bone Neoplasms
Prednisone
Antineoplastic Agents, Hormonal
Antineoplastic Combined Chemotherapy Protocols
Disease-Free Survival
Treatment Outcome
Proportional Hazards Models
Odds Ratio
Risk Factors
Retrospective Studies
Time Factors
Aged
Middle Aged
Male
Bone Density Conservation Agents
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Clinical Trials, Phase III as Topic
Kaplan-Meier Estimate
Bisphosphonate-Associated Osteonecrosis of the Jaw
Prostatic Neoplasms, Castration-Resistant
Steroid Synthesis Inhibitors
Abiraterone Acetate
Research team
Prostate Cancer Targeted Therapy Group
Language
eng
Date accepted
2015-04-21
License start date
2015-10
Citation
European urology, 2015, 68 (4), pp. 570 - 577
Publisher
ELSEVIER SCIENCE BV