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.
Author(s): Basch E(1), Autio K, Ryan CJ, Mulders P, Shore N, Kheoh T, Fizazi K, Logothetis
CJ, Rathkopf D, Smith MR, Mainwaring PN, Hao Y, Griffin T, Li S, Meyers ML,
Molina A, Cleeland C.
Affiliation(s): Author information:
(1)Department of Medicine, The University of North Carolina at Chapel Hill, Chapel
Hill, NC, USA. Electronic address: ebasch@med.unc.edu.
Publication date & source: 2013, Lancet Oncol. , 14(12):1193-9
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.
FINDINGS: 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).
INTERPRETATION: 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.
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