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document
Effect of enzalutamide on health-related quality of life , pain , and skeletal-related events in asymptomatic and minimally symptomatic , chemotherapy-naive patients with metastatic castration-resistant prostate cancer ( PREVAIL ) : results from a randomised , phase 3 trial . BACKGROUND Enzalutamide significantly increased overall survival and radiographic progression-free survival compared with placebo in the PREVAIL trial of asymptomatic and minimally symptomatic , chemotherapy-naive patients with metastatic castration-resistant prostate cancer . We report the effect of enzalutamide on health-related quality of life ( HRQoL ) , pain , and skeletal-related events observed during this trial . METHODS In this phase 3 , double-blind trial , patients were randomly assigned ( 1:1 ) to receive enzalutamide 160 mg/day ( n=872 ) or placebo ( n=845 ) orally . HRQoL was assessed at baseline and during treatment using the Functional Assessment of Cancer Therapy-Prostate ( FACT-P ) and EQ-5D questionnaires . Pain status was assessed at screening , baseline , week 13 , and week 25 with the Brief Pain Inventory Short Form ( BPI-SF ) . The primary analysis of HRQoL data used a mixed-effects model to test the difference between least square means change from baseline at week 61 . We assessed change from baseline , percentage improvement , and time to deterioration in HRQoL and pain , the proportion of patients with a skeletal-related event , and time to first skeletal-related event . Analysis was done on the intention-to-treat population . This study is registered with ClinicalTrials.gov , number NCT01212991 . FINDINGS Median treatment duration was 16·6 months ( IQR 10·1-21·1 ) in the enzalutamide group and 4·6 months ( 2·8-9·7 ) in the placebo group . The mixed-effects model analyses showed significant treatment differences in change from baseline to week 61 with enzalutamide compared with placebo for most FACT-P endpoints and EQ-5D visual analogue scale . Median time to deterioration in FACT-P total score was 11·3 months ( 95 % CI 11·1-13·9 ) in the enzalutamide group and 5·6 months ( 5·5-5·6 ) in the placebo groups ( hazard ratio [ HR ] 0·62 [ 95 % CI 0·54-0·72 ] ; p < 0·0001 ) . A significantly greater proportion of patients in the enzalutamide group than in the placebo group reported clinically meaningful improvements in FACT-P total score ( 327 [ 40 % ] of 826 vs 181 [ 23 % ] of 790 ) , in EQ-5D utility index ( 224 [ 28 % ] of 812 vs 99 [ 16 % ] of 623 ) , and visual analogue scale ( 218 [ 27 % ] of 803 vs 106 of [ 18 % ] 603 ; all p < 0·0001 ) . Median time to progression in BPI-SF pain at its worst was 5·7 months ( 95 % CI 5·6-5·7 ) in the enzalutamide group and 5·6 months ( 5·4-5·6 ) in the placebo group ( HR 0·62 [ 95 % CI 0·53-0·74 ] ; p < 0·0001 ) . Progression of pain at its worst was less common in the enzalutamide group than in the placebo group at week 13 ( 220 [ 29 % ] of 769 vs 257 [ 42 % ] of 610 ; p < 0·0001 ) , but not at week 25 ( 225 [ 32 % ] of 705 vs 135 [ 38 % ] of 360 ; p=0·068 ) . 278 ( 32 % ) of 872 patients in the enzalutamide group and 309 ( 37 % ) of 845 patients in the placebo group had experienced a skeletal-related event by data cutoff . Median time to first skeletal-related events in the enzalutamide group was 31·1 months ( 95 % CI 29·5-not reached ) and 31·3 months ( 95 % CI 23·9-not reached ) in the placebo group ( HR 0·72 [ 95 % CI 0·61-0·84 ] ; p < 0·0001 ) . INTERPRETATION In addition to improving overall survival relative to placebo , enzalutamide significantly improves patient-related outcomes and delays occurrence of first skeletal-related event in chemotherapy-naive men with metastatic castration-resistant prostate cancer . FUNDING Astellas Pharma and Medivation .
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Intervention_Pharmacological
enzalutamide
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Intervention_Pharmacological
Enzalutamide
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Intervention_Control
placebo
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Intervention_Pharmacological
enzalutamide
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Intervention_Pharmacological
enzalutamide 160 mg/day
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Intervention_Control
or placebo
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Outcome_Pain
health-related quality of life , pain , and skeletal-related events
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Outcome_Physical
overall survival
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Outcome_Physical
radiographic progression-free survival
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Outcome_Physical
health-related quality of life ( HRQoL )
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Outcome_Pain
pain
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Outcome_Physical
skeletal-related events
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Outcome_Physical
HRQoL
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Outcome_Pain
Pain status
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Outcome_Pain
Brief Pain Inventory Short Form ( BPI-SF ) .
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Outcome_Physical
primary analysis of HRQoL data
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Outcome_Physical
change from baseline
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Outcome_Physical
percentage improvement
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Outcome_Physical
time to deterioration in HRQoL and pain
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Outcome_Mental
proportion of patients with a skeletal-related event
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Outcome_Mental
time to first skeletal-related event
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Outcome_Mental
Median treatment duration
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Outcome_Mental
significant treatment differences
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Outcome_Other
endpoints and EQ-5D visual analogue scale
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Outcome_Other
Median time to deterioration in FACT-P total
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Outcome_Other
improvements in FACT-P
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Outcome_Other
[ 23 % ] of 790 ) , in EQ-5D
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Outcome_Other
[ 16 % ] of 623 ) , and visual
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Outcome_Other
603 ; all p < 0·0001 )
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Outcome_Other
CI 0·53-0·74 ] ; p < 0·0001 )
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Outcome_Other
placebo group had experienced
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Outcome_Mental
skeletal-related event by data cutoff
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Outcome_Other
Median time to first
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Outcome_Mental
INTERPRETATION In addition
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Outcome_Other
enzalutamide significantly improves patient-related outcomes and delays occurrence
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Participant_Condition
asymptomatic and minimally symptomatic , chemotherapy-naive patients with metastatic castration-resistant prostate cancer ( PREVAIL
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Participant_Condition
asymptomatic and minimally symptomatic
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Participant_Condition
chemotherapy-naive patients with metastatic castration-resistant prostate cancer
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Participant_Condition
patients were randomly assigned ( 1:1 ) to
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Participant_Condition
or
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Participant_Condition
occurrence of first skeletal-related event in chemotherapy-naive
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Participant_Sex
men
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Participant_Condition
with metastatic