Abiraterone acetate plus prednisone versus prednisone alone in chemotherapy-naive men with metastatic castration-resistant prostate cancer: patient-reported outcome results of a randomised phase 3 trial.
BACKGROUND
Abiraterone acetate plus prednisone significantly improves radiographic progression-free survival in asymptomatic or mildly symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer compared with prednisone alone. We describe analyses of data for patient-reported pain and functional status in a preplanned interim analysis of a phase 3 trial.


METHODS
Between April 28, 2009, and June 23, 2010, patients with progressive, metastatic castration-resistant prostate cancer were enrolled into a multinational, double-blind, placebo-controlled trial. Patients were eligible if they were asymptomatic (score of 0 or 1 on item three of the Brief Pain Inventory Short Form [BPI-SF] questionnaire) or mildly symptomatic (score of 2 or 3) and had not previously received chemotherapy. Patients were randomly assigned (1:1) to receive oral abiraterone (1 g daily) plus prednisone (5 mg twice daily) or placebo plus prednisone in continuous 4-week cycles. Pain was assessed with the BPI-SF questionnaire, and health-related quality of life (HRQoL) with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. We analysed data with prespecified criteria for clinically meaningful pain progression and deterioration in HRQoL. All patients who underwent randomisation were included in analyses.


RESULTS
1088 patients underwent randomisation: 546 were assigned to abiraterone plus prednisone and 542 to placebo plus prednisone. At the time of the second prespecified interim analysis, median follow-up was 22·2 months (IQR 20·2-24·8). Median time to progression of mean pain intensity was longer in patients assigned to abiraterone plus prednisone (26·7 months [95% CI 19·3-not estimable]) than in those assigned to placebo plus prednisone (18·4 months [14·9-not estimable]; hazard ratio [HR] 0·82, 95% CI 0·67-1·00; p=0·0490), as was median time to progression of pain interference with daily activities (10·3 months [95% CI 9·3-13·0] vs 7·4 months [6·4-8·6]; HR 0·79, 95% CI 0·67-0·93; p=0·005). Median time to progression of worst pain was also longer with abiraterone plus prednisone (26·7 months [95% CI 19·4-not estimable]) than with placebo plus prednisone (19·4 months [16·6-not estimable]), but the difference was not significant (HR 0·85, 95% CI 0·69-1·04; p=0·109). Median time to HRQoL deterioration was longer in patients assigned to abiraterone plus prednisone than in those assigned to placebo plus prednisone as assessed by the FACT-P total score (12·7 months [95% CI 11·1-14·0] vs 8·3 months [7·4-10·6]; HR 0·78, 95% CI 0·66-0·92; p=0·003) and by the score on its prostate-cancer-specific subscale (11·1 months [8·6-13·8] vs 5·8 months [5·5-8·3]; HR 0·70, 95% CI 0·60-0·83; p<0·0001).


CONCLUSIONS
Abiraterone plus prednisone delays patient-reported pain progression and HRQoL deterioration in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. These results provide further support for the efficacy of abiraterone in this population.
Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: ebasch@med.unc.edu.
Ethan
E
Basch
Karen
K
Autio
Charles J
CJ
Ryan
Peter
P
Mulders
Neal
N
Shore
Thian
T
Kheoh
Karim
K
Fizazi
Christopher J
CJ
Logothetis
Dana
D
Rathkopf
Matthew R
MR
Smith
Paul N
PN
Mainwaring
Yanni
Y
Hao
Thomas
T
Griffin
Susan
S
Li
Michael L
ML
Meyers
Arturo
A
Molina
Charles
C
Cleeland
D000069501:Abiraterone Acetate; D000203:Activities of Daily Living; D000730:Androstadienes / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001315:Australia; D002170:Canada; D017281:Cost of Illness; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005060:Europe; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D010146:Pain / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D010147:Pain Measurement; D011241:Prednisone / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D064129:Prostatic Neoplasms, Castration-Resistant / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D000730:Androstadienes; D000069501:Abiraterone Acetate; D011241:Prednisone