***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 Olaparib is a poly(ADP-ribose ) polymerase inhibitor and cediranib is an anti-angiogenic agent with activity against VEGF receptor ( VEGFR ) 1 , VEGFR2 , and VEGFR3 . Both oral agents have antitumour activity in women with recurrent ovarian cancer , and their combination was active and had manageable toxicities in a phase 1 trial . We investigated whether this combination could improve progression-free survival ( PFS ) compared with olaparib monotherapy in women with recurrent platinum-sensitive ovarian cancer . METHODS In our r and omised , open-label , phase 2 study , we recruited women ( aged ≥18 years ) who had measurable platinum-sensitive , relapsed , high- grade serous or endometrioid ovarian , fallopian tube , or primary peritoneal cancer , or those with deleterious germline BRCA1/2 mutations from nine participating US academic medical centres . We r and omly allocated participants ( 1:1 ) according to permuted blocks , stratified by germline BRCA status and previous anti-angiogenic therapy , to receive olaparib capsules 400 mg twice daily or the combination at the recommended phase 2 dose of cediranib 30 mg daily and olaparib capsules 200 mg twice daily . The primary endpoint was progression-free survival analysed in the intention-to-treat population . The phase 2 trial is no longer accruing patients . An interim analysis was conducted in November , 2013 , after 50 % of expected events had occurred and efficacy results were unmasked . The primary analysis was performed on March 31 , 2014 , after 47 events ( 66 % of those expected ) . The trial is registered with Clinical Trials.gov , number NCT01116648 . FINDINGS Between Oct 26 , 2011 , and June 3 , 2013 , we r and omly allocated 46 women to receive olaparib alone and 44 to  receive the combination of olaparib and cediranib  . Median PFS was 17·7 months ( 95 % CI 14·7-not reached ) for the women treated with cediranib plus olaparib compared with 9·0 months ( 95 % CI 5·7 - 16·5 ) for those treated with olaparib monotherapy ( hazard ratio 0·42 , 95 % CI 0·23 - 0·76 ; p=0·005 ) . Grade 3 and 4 adverse events were more common with combination therapy than with monotherapy , including fatigue ( 12 patients in the cediranib plus olaparib group vs five patients in the olaparib monotherapy group ) , diarrhoea ( ten vs none ) , and hypertension ( 18 vs none ) . INTERPRETATION Cediranib plus olaparib seems to improve PFS  in women with recurrent platinum-sensitive high- grade serous or endometrioid ovarian cancer , and warrants study in a phase 3 trial . The side-effect profile suggests such investigations should include assessment s of quality of life and patient-reported outcomes to underst and the effects of a continuing oral regimen with that of intermittent chemotherapy . FUNDING American Recovery and Reinvestment Act grant from the National Institutes of Health ( NIH ) ( 3 U01 CA062490 - 16S2 ) ; Intramural Program of the Center for Cancer Research ; and the Division of Cancer Treatment and Diagnosis , National Cancer Institute , NIH BACKGROUND Olaparib ( AZD2281 ) is an oral poly(adenosine diphosphate [ADP]-ribose ) polymerase inhibitor that has shown antitumor activity in patients with high- grade serous ovarian cancer with or without BRCA1 or BRCA2 germline mutations . METHODS We conducted a r and omized , double-blind , placebo-controlled , phase 2 study to evaluate maintenance treatment with olaparib in patients with platinum-sensitive , relapsed , high- grade serous ovarian cancer who had received two or more platinum-based regimens and had had a partial or complete response to their most recent platinum-based regimen . Patients were r and omly assigned to receive olaparib , at a dose of 400 mg twice daily , or placebo . The primary end point was progression-free survival according to the Response Evaluation Criteria in Solid Tumors guidelines . RESULTS Of 265 patients who underwent r and omization , 136 were assigned to the olaparib group and 129 to the placebo group .  Progression-free survival was significantly longer with olaparib than with placebo ( median , 8.4 months vs. 4.8 months from r and omization on completion of chemotherapy ; hazard ratio for progression or death , 0.35 ; 95 % confidence interval [ CI ] , 0.25 to 0.49 ; P<0.001 ) . Subgroup analyses of progression-free survival showed that , regardless of subgroup , patients in the olaparib group had a lower risk of progression . Adverse events more commonly reported in the olaparib group than in the placebo group ( by more than 10 % of patients ) were nausea ( 68 % vs. 35 % ) , fatigue ( 49 % vs. 38 % ) , vomiting ( 32 % vs. 14 % ) , and anemia ( 17 % vs. 5 % ) ; the majority of adverse events were grade 1 or 2 . An interim analysis of overall survival ( 38 % maturity , meaning that 38 % of the patients had died ) showed no significant difference between groups ( hazard ratio with olaparib , 0.94 ; 95 % CI , 0.63 to 1.39 ; P=0.75 ) . CONCLUSIONS Olaparib as maintenance treatment significantly improved progression-free survival among patients with platinum-sensitive , relapsed , high- grade serous ovarian cancer . Interim analysis showed no overall survival benefit . The toxicity profile of olaparib in this population was consistent with that in previous studies . ( Funded by AstraZeneca ; Clinical Trials.gov number , NCT00753545 . ) BACKGROUND The inhibition of poly(adenosine diphosphate [ADP]-ribose ) polymerase ( PARP ) is a potential synthetic lethal therapeutic strategy for the treatment of cancers with specific DNA-repair defects , including those arising in carriers of a BRCA1 or BRCA2 mutation . We conducted a clinical evaluation in humans of olaparib ( AZD2281 ) , a novel , potent , orally active PARP inhibitor . METHODS This was a phase 1 trial that included the analysis of pharmacokinetic and pharmacodynamic characteristics of olaparib . Selection was aim ed at having a study population enriched in carriers of a BRCA1 or BRCA2 mutation . RESULTS We enrolled and treated 60 patients ; 22 were carriers of a BRCA1 or BRCA2 mutation and 1 had a strong family history of BRCA-associated cancer but declined to undergo mutational testing . The olaparib dose and schedule were increased from 10 mg daily for 2 of every 3 weeks to 600 mg twice daily continuously . Reversible dose-limiting toxicity was seen in one of eight patients receiving 400 mg twice daily ( grade 3 mood alteration and fatigue ) and two of five patients receiving 600 mg twice daily ( grade 4 thrombocytopenia and grade 3 somnolence ) . This led us to enroll another cohort , consisting only of carriers of a BRCA1 or BRCA2 mutation , to receive olaparib at a dose of 200 mg twice daily . Other adverse effects included mild gastrointestinal symptoms . There was no obvious increase in adverse effects seen in the mutation carriers . Pharmacokinetic data indicated rapid absorption and elimination ; pharmacodynamic studies confirmed PARP inhibition in surrogate sample s ( of peripheral-blood mononuclear cells and plucked eyebrow-hair follicles ) and tumor tissue . Objective antitumor activity was reported only in mutation carriers , all of whom had ovarian , breast , or prostate cancer and had received multiple treatment regimens . CONCLUSIONS Olaparib has few of the adverse effects of conventional chemotherapy , inhibits PARP , and has antitumor activity in cancer associated with the BRCA1 or BRCA2 mutation . ( Clinical Trials.gov number , NCT00516373 . Purpose : Veliparib , a PARP inhibitor , demonstrated clinical activity in combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors in a phase I trial . To define the relative contribution of PARP inhibition to the observed clinical activity , we conducted a r and omized phase II trial to determine the response rate of veliparib in combination with cyclophosphamide compared with cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or in patients with pretreated primary peritoneal , fallopian tube , or high- grade serous ovarian cancers ( HGSOC ) . Experimental Design : Adult patients were r and omized to receive cyclophosphamide alone ( 50 mg orally once daily ) or with veliparib ( 60 mg orally once daily ) in 21-day cycles . Crossover to the combination was allowed at disease progression . Results : Seventy-five patients were enrolled and 72 were evaluable for response ; 38 received cyclophosphamide alone and 37 the combination as their initial treatment regimen . Treatment was well tolerated . One complete response was observed in each arm , with three partial responses ( PR ) in the combination arm and six PRs in the cyclophosphamide alone arm . Genetic sequence and expression analyses were performed for 211 genes involved in DNA repair ; none of the detected genetic alterations were significantly associated with treatment benefit . Conclusion : This is the first trial that evaluated single-agent , low-dose cyclophosphamide in HGSOC , peritoneal , fallopian tube , and BRCA-mutant ovarian cancers . It was well tolerated and clinical activity was observed ; the addition of veliparib at 60 mg daily did not improve either the response rate or the median progression-free survival . Clin Cancer Res ; 21(7 ) ; 1574–82 . © 2015 AACR 5003 Background : Olaparib ( AZD2281 ) is an oral PARP inhibitor that has shown antitumor activity in patients ( pts ) with high- grade serous ovarian cancer ( SOC ) with and without BRCA1 or BRCA2 mutations . This r and omized , double-blind , multicenter , placebo-controlled Phase II study evaluated maintenance treatment with olaparib in pts with high- grade PSR SOC ( clinical trials.gov ; NCT00753545 ) . METHODS Pts with PSR SOC who had received ≥2 previous platinum regimens and were in a maintained partial or complete response following their last platinum-containing regimen were r and omized to  oral olaparib 400 mg bid or placebo . The primary endpoint was progression-free survival ( PFS ) by RECIST . Secondary endpoints included time to progression ( TTP ) by CA-125 ( GCIG criteria ) or RECIST , overall survival ( OS ) and safety . RESULTS 265 pts were r and omized ( 136 to olaparib and 129 to placebo ) . Demographics and baseline characteristics were generally well balanced . At data cut-off there were 153 ( 58 % ) progression events . PFS by RECIST was significantly longer in the olaparib than the placebo group ( HR , 0.35 ; 95 % CI 0.25 - 0.49 ; P<0.00001 ; median 8.4 vs 4.8 months ) . TTP by CA-125 or RECIST was also significantly longer in the olaparib than the placebo group ( HR , 0.35 ; 95 % CI 0.25 - 0.47 ; P<0.00001 ; median 8.3 vs 3.7 months ) . At data cut-off OS data were too immature for analysis . 68 ( 50 % ) and 21 ( 16 % ) remain on olaparib or placebo , respectively . AEs more commonly reported on olaparib than placebo ( by > 10 % ) were nausea ( 68 % vs 35 % ) , fatigue ( 49 % vs 38 % ) , vomiting ( 32 % vs 14 % ) and anemia ( 17 % vs 5 % ) ; the majority of AEs were CTCAE grade 1 or 2 . The most frequently reported CTCAE grade ≥3 events were fatigue ( 9 pts ) and anemia ( 7 pts ) for olaparib , and abdominal pain and fatigue ( 4 pts each ) for placebo . 3 ( 2.2 % ) pts on olaparib and 1 ( 0.8 % ) on placebo had AEs that led to treatment discontinuation . 31 pts ( 23 % ) in the olaparib group and 9 ( 7 % ) in the placebo group had both dose reductions and interruptions . CONCLUSIONS In pts with PSR SOC , maintenance treatment with olaparib 400 mg bid provided a significant improvement in PFS . Olaparib was well tolerated , and 
    Output:
    
PARP inhibitors appear to improve PFS  in women with recurrent platinum-sensitive disease .
Ongoing studies are likely to provide more information about whether the improvement in PFS leads to any change in OS in this subgroup of women with EOC .
More research is needed to determine whether PARP inhibitors have any role to play in platinum-resistant disease