***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) BACKGROUND In the AFFIRM trial of patients with metastatic castration-resistant prostate cancer after progression with docetaxel treatment , enzalutamide significantly increased overall survival compared with placebo . Here we present the prospect ively defined analyses of some secondary endpoints , including occurrence of skeletal-related events , measures of pain control , and patient-reported health-related quality of life ( HRQoL ) . METHODS In this phase 3 , double-blind trial , patients were r and omly assigned ( 2:1 ) to receive enzalutamide 160 mg/day or placebo orally , stratified by ECOG baseline performance status ( 0 or 1 vs 2 ) and mean pain score ( Brief Pain Inventory-Short Form [ BPI-SF ] question 3 worst pain , score ≤3 vs ≥4 ) . Secondary endpoints were time to first skeletal-related event ( defined as radiation therapy or surgery to bone ) ; change from baseline to week 13 in pain severity and interference ; pain palliation and progression at week 13 ; time to pain progression ; overall improvement in HRQoL ; improvements in HRQoL domains ; and time to HRQoL deterioration . Analysis was done on the intention-to-treat population for each endpoint . AFFIRM is registered with Clinical Trials.gov , number NCT00974311 . FINDINGS Median time to first skeletal-related event in the enzalutamide ( n=800 ) and placebo ( n=399 ) groups was 16·7 months ( 95 % CI 14·6 to 19·1 ) and 13·3 months ( 95 % CI 9·9 to not yet reached ) , respectively ( hazard ratio [ HR ] 0·69 [ 95 % CI 0·57 - 0·84 ] ; p=0·0001 ) . Pain progression at week 13 occurred in 174 ( 28 % ) of 625 evaluable patients in the enzalutamide group versus 101 ( 39 % ) of 259 patients in the placebo group ( difference -11·2 % , 95 % CI -18·1 to -4·3 ; p=0·0018 ) . Median time to pain progression was not yet reached in the enzalutamide group ( 95 % CI not yet reached to not yet reached ) versus 13·8 ( 13·8 to not yet reached ) months in the placebo group ( HR 0·56 [ 95 % CI 0·41 to 0·78 ] ; p=0·0004 ) . Mean treatment effects for pain severity ( mean change from baseline in the enzalutamide group -0·15 , 95 % CI -0·28 to -0·02 , vs placebo 0·50 , 0·29 to 0·70 ; difference -0·65 , 95 % CI -0·89 to -0·41 ; p<0·0001 ) and interference ( -0·01 , -0·18 to 0·16 , vs 0·74 , 0·47 to 1·00 ; respectively , difference -0·74 , 95 % -1·06 to -0·43 ; p<0·0001 ) were significantly better with enzalutamide than with placebo . 22 ( 45 % ) of 49 evaluable patients in the enzalutamide  group reported pain palliation at week 13 versus one ( 7 % ) of 15 in the placebo group ( difference 38·2 % , 95 % CI 19·4 - 57·0 ; p=0·0079 ) . Overall improvement in HRQoL was reported in more patients receiving enzalutamide ( 275 [ 42 % ] of 652 ) than in those receiving placebo ( 36 [ 15 % ] of 248 ; p<0·0001 ) . Patients in the enzalutamide group had longer median time to HRQoL deterioration than did those in the placebo group ( 9·0 months , 95 % CI 8·3 - 11·1 , vs 3·7 months , 95 % CI 3·0 - 4·2 ; HR 0·45 , 95 % CI 0·37 - 0·55 ; p<0·0001 ) in risk of deterioration . INTERPRETATION Our results show that , in addition to improving overall survival , enzalutamide  improves wellbeing and everyday functioning of patients with metastatic castration-resistant prostate cancer . FUNDING Astellas Pharma and Medivation 
    Output:
    
With regard to the effectiveness of Enz following AA or AA following Enz , recent retrospective case series reported overall survival and secondary endpoints for patients with mCRPC progression after chemotherapy .