***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 . ) Primary resistance to and rogen receptor (AR)-directed therapies in metastatic castration-resistant prostate cancer ( mCRPC ) is poorly understood . We r and omized 202 patients with treatment-naïve mCRPC to abiraterone or enzalutamide  and performed whole-exome and deep targeted 72-gene sequencing of plasma cell-free DNA prior to therapy . For these agents , which have never been directly compared , time to progression was similar . Defects in BRCA2 and ATM were strongly associated with poor clinical outcomes independently of clinical prognostic factors and circulating tumor DNA abundance . Somatic alterations in TP53 , previously linked to reduced tumor dependency on AR signaling , were also independently associated with rapid resistance . Although detection of AR amplifications did not outperform st and ard prognostic biomarkers , AR gene structural rearrangements truncating the lig and binding domain were identified in several patients with primary resistance . These findings establish genomic drivers of resistance to first-line AR-directed therapy in mCRPC and identify potential minimally invasive biomarkers . Significance : Leveraging plasma specimens collected in a large r and omized phase II trial , we report the relative impact of common circulating tumor DNA alterations on patient response to the most widely used therapies for advanced prostate cancer . Our findings suggest that liquid biopsy analysis can guide the use of AR-targeted therapy in general practice . Cancer Discov ; 8(4 ) ; 444 - 57 . © 2018 AACR.See related commentary by Jayaram et al. , p. 392This article is highlighted in the In This Issue feature , p. 371 PURPOSE Persistent and rogen signaling is implicated in castrate-resistant prostate cancer ( CRPC ) progression . This study aim ed to evaluate and rogen signaling in bone marrow-infiltrating cancer and testosterone in blood and bone marrow and to correlate with clinical observations . PATIENTS AND METHODS This was an open-label , observational study of 57 patients with bone-metastatic CRPC who underwent transiliac bone marrow biopsy between October 2007 and March 2010 . Patients received oral abiraterone acetate ( 1 g ) once daily and prednisone ( 5 mg ) twice daily . And rogen receptor ( AR ) and CYP17 expression were assessed by immunohistochemistry , testosterone concentration by mass spectrometry , AR copy number by polymerase chain reaction , and TMPRSS2-ERG status by fluorescent in situ hybridization in available tissues . RESULTS Median overall survival was 555 days ( 95 % CI , 440 to 965 + days ) . Maximal prostate-specific antigen decline ≥ 50 % occurred in 28 ( 50 % ) of 56 patients . Homogeneous , intense nuclear expression of AR , combined with ≥ 10 % CYP17 tumor expression , was correlated with longer time to treatment discontinuation ( > 4 months ) in 25 patients with tumor-infiltrated bone marrow sample s. Pretreatment CYP17 tumor expression ≥ 10 % was correlated with increased bone marrow aspirate testosterone . Blood and bone marrow aspirate testosterone concentrations declined to less than picograms-per-milliliter levels and remained suppressed at progression . CONCLUSION The observed pretreatment and rogen-signaling signature is consistent with persistent and rogen signaling in CRPC bone metastases . This is the first evidence that abiraterone acetate  achieves sustained suppression of testosterone in both blood and bone marrow aspirate to less than picograms-per-milliliter levels . Potential admixture of blood with bone marrow aspirate limits our ability to determine the origin of measured testosterone 
    Output:
    
ABI-to-ENZ sequential therapy in patients with CRPC was associated with better PFS , PSA – PFS , and PSA response rates .
Regardless of sequencing , response to drug therapy was transient for both ABI and ENZ when either agent was used as a secondary therapy .