You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial
Abstract 1:
Summary Background Long-term hormone therapy has been the st and ard of care for advanced prostate cancer since the 1940s . STAMPEDE is a r and omised controlled trial using a multiarm , multistage platform design . It recruits men with high-risk , locally advanced , metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy .  We report primary survival results for three research comparisons testing the addition of zoledronic acid , docetaxel , or their combination to st and ard of care versus st and ard of care alone . Methods St and ard of care was hormone therapy for at least 2 years ; radiotherapy was encouraged for men with N0M0 disease to November , 2011 , then m and ated ; radiotherapy was optional for men with node-positive non-metastatic ( N+M0 ) disease . Stratified r and omisation ( via minimisation ) allocated men 2:1:1:1 to st and ard of care only ( SOC-only ; control ) , st and ard of care plus zoledronic acid ( SOC + ZA ) , st and ard of care plus docetaxel ( SOC + Doc ) , or st and ard of care with both zoledronic acid and docetaxel ( SOC + ZA + Doc ) . Zoledronic acid ( 4 mg ) was given for six 3-weekly cycles , then 4-weekly until 2 years , and docetaxel ( 75 mg/m2 ) for six 3-weekly cycles with prednisolone 10 mg daily . There was no blinding to treatment allocation . The primary outcome measure was overall survival . Pairwise comparisons of research versus control had 90 % power at 2·5 % one-sided α for hazard ratio ( HR ) 0·75 , requiring roughly 400 control arm deaths . Statistical analyses were undertaken with st and ard log-rank-type methods for time-to-event data , with hazard ratios ( HRs ) and 95 % CIs derived from adjusted Cox models . This trial is registered at Clinical Trials.gov ( NCT00268476 ) and ControlledTrials.com ( IS RCT N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy  , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade 3–5 adverse events were reported for 399 ( 32 % ) patients receiving SOC , 197 ( 32 % ) receiving SOC + ZA , 288 ( 52 % ) receiving SOC + Doc , and 269 ( 52 % ) receiving SOC + ZA + Doc . Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of st and ard of care for this population . Docetaxel chemotherapy , given at the time of long-term hormone therapy initiation , showed evidence of improved survival accompanied by an increase in adverse events . Docetaxel treatment should become part of st and ard of care for adequately fit men commencing  long-term hormone  therapy . Funding Cancer Research UK , Medical Research Council , Novartis , Sanofi-Aventis , Pfizer , Janssen , Astellas , NIHR Clinical Research Network , Swiss Group for Clinical Cancer Research


Title 2:
Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy
Abstract 2:
Background Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer . We assessed the effect of this combination in men starting long‐term and rogen‐deprivation therapy ( ADT ) , using a multigroup , multistage trial design . Methods We r and omly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate ( 1000 mg daily ) and prednisolone ( 5 mg daily ) ( combination therapy ) . Local radiotherapy was m and ated for patients with node‐negative , nonmetastatic disease and encouraged for those with positive nodes . For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease , treatment continued until radiologic , clinical , or prostate‐specific antigen ( PSA ) progression ; otherwise , treatment was to continue for 2 years or until any type of progression , whichever came first . The primary outcome measure was overall survival . The intermediate primary outcome was failure‐free survival ( treatment failure was defined as radiologic , clinical , or PSA progression or death from prostate cancer ) . Results A total of 1917 patients underwent r and omization from November 2011 through January 2014 . The median age was 67 years , and the median PSA level was 53 ng per milliliter . A total of 52 % of the patients had metastatic disease , 20 % had node‐positive or node‐indeterminate nonmetastatic disease , and 28 % had node‐negative , nonmetastatic disease ; 95 % had newly diagnosed disease . The median follow‐up was 40 months . There were 184 deaths in the combination group as compared with 262 in the ADT‐alone group ( hazard ratio , 0.63 ; 95 % confidence interval [ CI ] , 0.52 to 0.76 ; P<0.001 ) ; the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease . There were 248 treatment‐failure events in the combination group as compared with 535 in the ADT‐alone group ( hazard ratio , 0.29 ; 95 % CI , 0.25 to 0.34 ; P<0.001 ) ; the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease . Grade 3 to 5 adverse events occurred in 47 % of the patients in the combination group ( with nine grade 5 events ) and in 33 % of the patients in the ADT‐alone group ( with three grade 5 events ) . Conclusions Among men with locally advanced or metastatic prostate cancer  , ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure‐free survival than ADT alone . ( Funded by Cancer Research U.K. and others ; STAMPEDE Clinical Trials.gov number , NCT00268476 , and Current Controlled Trials number , IS RCT N78818544 .
Olaparib has been the first agent showing a benefit in terms of rPFS and ORR alone or in combination with abiraterone plus prednisone in patients with DDR deficiency prostate cancer .