***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 Treatment options for recurrent glioblastoma are scarce , with second-line chemotherapy showing only modest activity against the tumour . Despite the absence of well controlled trials , bevacizumab is widely used in the treatment of recurrent glioblastoma . Nonetheless , whether the high response rates reported after treatment with this drug translate into an overall survival benefit remains unclear . We report the results of the first r and omised controlled phase 2 trial of bevacizumab in recurrent glioblastoma . METHODS The BELOB trial was an open-label , three-group , multicentre phase 2 study undertaken in 14 hospitals in the Netherl and s. Adult patients ( ≥18 years of age ) with a first recurrence of a glioblastoma after temozolomide chemoradiotherapy  were r and omly allocated by a web-based program to treatment with oral lomustine 110 mg/m(2 ) once every 6 weeks , intravenous bevacizumab 10 mg/kg once every 2 weeks , or combination treatment with lomustine 110 mg/m(2 ) every 6 weeks and bevacizumab 10 mg/kg every 2 weeks . R and omisation of patients was stratified with a minimisation procedure , in which the stratification factors were centre , Eastern Cooperative Oncology Group performance status , and age . The primary outcome was overall survival at 9 months , analysed by intention to treat . A safety analysis was planned after the first ten patients completed two cycles of 6 weeks in the combination treatment group . This trial is registered with the Nederl and s Trial Register ( www.trialregister.nl , number NTR1929 ) . FINDINGS Between Dec 11 , 2009 , and Nov 10 , 2011 , 153 patients were enrolled . The preplanned safety analysis was done after eight patients had been treated , because of haematological adverse events ( three patients had grade 3 thrombocytopenia and two had grade 4 thrombocytopenia ) which reduced bevacizumab dose intensity ; the lomustine dose in the combination treatment group was thereafter reduced to 90 mg/m(2 ) . Thus , in addition to the eight patients who were r and omly assigned to receive bevacizumab plus lomustine 110 mg/m(2 ) , 51 patients were assigned to receive bevacizumab alone , 47 to receive lomustine alone , and 47 to receive bevacizumab plus lomustine 90 mg/m(2 ) . Of these patients , 50 in the bevacizumab alone group , 46 in the lomustine alone group , and 44 in the bevacizumab and lomustine 90 mg/m(2 ) group were eligible for analyses . 9-month overall survival was 43 % ( 95 % CI 29 - 57 ) in the lomustine group , 38 % ( 25 - 51 ) in the bevacizumab group , 59 % ( 43 - 72 ) in the bevacizumab and lomustine 90 mg/m(2 ) group , 87 % ( 39 - 98 ) in the bevacizumab and lomustine 110 mg/m(2 ) group , and 63 % ( 49 - 75 ) for the combined bevacizumab and lomustine groups . After the reduction in lomustine dose in the combination group , the combined treatment was well tolerated . The most frequent grade 3 or worse toxicities were hypertension ( 13 [ 26 % ] of 50 patients in the bevacizumab group , three [ 7 % ] of 46 in the lomustine group , and 11 [ 25 % ] of 44 in the bevacizumab and lomustine 90 mg/m(2 ) group ) , fatigue ( two [ 4 % ] , four [ 9 % ] , and eight [ 18 % ] ) , and infections ( three [ 6 % ] , two [ 4 % ] , and five [ 11 % ] ) . At the time of this analysis , 144/148 ( 97 % ) of patients had died and three ( 2 % ) were still on treatment . INTERPRETATION The combination of bevacizumab and lomustine met prespecified criteria for assessment of this treatment in further phase 3 studies . However , the results in the bevacizumab alone group do not justify further studies of this treatment . FUNDING Roche Nederl and and KWF Kankerbestrijding Background The addition of bevacizumab to temozolomide-based chemoradiotherapy ( TMZ/RT → TMZ ) did not prolong overall survival ( OS ) in patients with newly diagnosed glioblastoma in phase III trials . Elderly and frail patients are underrepresented in clinical trials , but early reports suggested preferential benefit in this population . Patients and methods ARTE was a 2 : 1 r and omized , multi-center , open-label , non-comparative phase II trial of hypofractionated RT ( 40 Gy in 15 fractions ) with bevacizumab ( 10 mg/kg × 14 days ) ( arm A , N = 50 ) or without bevacizumab ( arm B , N = 25 ) in patients with newly diagnosed glioblastoma aged ≥65 years . The primary objective was to obtain evidence for prolongation of median OS by the addition of bevacizumab to RT . Response was assessed by RANO criteria . Quality of life ( QoL ) was monitored by the EORTC QLQ-C30/BN20 modules . Exploratory studies included molecular subtyping by 450k whole methylome and gene expression analyses . Results Median PFS was longer in arm A than in arm B ( 7.6 and 4.8 months , P = 0.003 ) , but OS was similar ( 12.1 and 12.2 months , P = 0.77 ) . Clinical deterioration was delayed and more patients came off steroids in arm A. Prolonged PFS in arm A was confined to tumors with the receptor tyrosine kinase ( RTK ) I methylation subtype ( HR 0.25 , P = 0.014 ) and proneural gene expression ( HR 0.29 , P = 0.025 ) . In a Cox model of OS controlling for established prognostic factors , associations with more favorable outcome were identified for age < 70 years ( HR 0.52 , P = 0.018 ) and Karnofsky performance score 90%-100 % ( HR 0.51 , P = 0.026 ) . Including molecular subtypes into that model identified an association of the RTK II gene methylation subtype with inferior OS ( HR 1.73 , P = 0.076 ) . Conclusion Efficacy outcomes and exploratory analyses of ARTE do not support the hypothesis that the addition of bevacizumab to RT generally prolongs survival in elderly glioblastoma patients . Molecular biomarkers may identify patients with preferential benefit from bevacizumab . Clinical trial registration number NCT01443676 In recurrent glioblastoma , health-related quality of life ( HRQL ) is a crucial trial endpoint . We examined HRQL outcomes as a secondary endpoint for patients in the CABARET r and omized phase 2 trial . 122 patients were r and omly allocated to bevacizumab monotherapy or bevacizumab plus carboplatin .  We calculated change scores from baseline for each HRQL measure on the European Organisation for Research and Treatment of Cancer Quality of Life Question naire Core 30 ( EORTC QLQ-C30 ) and the Brain Cancer Module ( QLQ-BN20 ) , together with time to deterioration in HRQL , and the proportion of participants with clinical ly meaningful improvements in specific disease-related symptoms . At baseline , 117 of 122 r and omized patients ( 96 % ) attempted question naires . Question naire participation rates were > 90 % for patients continuing on treatment , however at the end-of-treatment visit only 72 ( 64 % of eligible participants ) returned a form . There were no differences between arms in change scores over the treatment period . Time to ≥10 point deterioration in scores from baseline was also similar between arms . HRQL deterioration occurred largely before progression for the domains tested , but scores in HRQL domains specifically relevant to symptoms of recurrent glioblastoma also improved for about 50 % of patients with symptoms at baseline . Neither detrimental nor beneficial effects on HRQL were seen with carboplatin added to bevacizumab , with a proportion of patients on both arms experiencing symptomatic benefit . Given the reduced question naire completion at end of treatment , time to HRQL deterioration is a feasible and robust clinical trial endpoint in this patient population . Clinical trials registration number : ACTRN12610000915055 BACKGROUND Survival outcomes for patients with glioblastoma remain poor , particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase ( MGMT ) gene promoter . This phase II , r and omized , open-label , multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with st and ard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter . METHODS Overall , 265 patients were r and omized ( 1:1:1 ) to st and ard cilengitide ( 2000 mg 2 × /wk ; n = 88 ) , intensive cilengitide ( 2000 mg 5 × /wk during wk 1 - 6 , thereafter 2 × /wk ; n = 88 ) , or a control arm ( chemoradiotherapy alone ; n = 89 ) . Cilengitide was administered intravenously in combination with daily temozolomide ( TMZ ) and concomitant radiotherapy ( RT ; wk 1 - 6 ) , followed by TMZ maintenance therapy ( TMZ/RT→TMZ ) . The primary endpoint was overall survival ; secondary endpoints included progression-free survival , pharmacokinetics , and safety and tolerability . RESULTS Median overall survival was 16.3 months in the st and ard cilengitide arm ( hazard ratio [ HR ] , 0.686 ; 95 % CI : 0.484 , 0.972 ; P = .032 ) and 14.5 months in the intensive cilengitide arm ( HR , 0.858 ; 95 % CI : 0.612 , 1.204 ; P = .3771 ) versus 13.4 months in the control arm . Median progression-free survival assessed per independent review committee was 5.6 months ( HR , 0.822 ; 95 % CI : 0.595 , 1.134 ) and 5.9 months ( HR , 0.794 ; 95 % CI : 0.575 , 1.096 ) in the st and ard and intensive cilengitide arms , respectively , versus 4.1 months in the control arm . Cilengitide was well tolerated . CONCLUSIONS St and ard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ . Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study BACKGROUND Few prospect i ve studies have assessed the role of bevacizumab and included a control arm with st and ard treatments for recurrent glioblastoma . We conducted a noncomparative phase II trial ( AVAREG ) to examine the efficacy of bevacizumab or fotemustine in this setting . METHODS Eligible patients were r and omized 2:1 to receive  bevacizumab  ( 10 mg/kg every 2 weeks ) or fotemustine ( 75 mg/m(2 ) on days 1 , 8 , and 15 , then 100 mg/m(2 ) every 3 weeks after a 35-day interval ) . The primary endpoint was 6-month overall survival ( OS ) rate ( OS-6 ) . No formal efficacy comparison was made between the treatment arms . RESULTS Ninety-one patients were enrolled ( bevacizumab n = 59 ; fotemustine n = 32 ) . Median age was 57 years ( range , 28 - 78 y ) , and patients had Eastern Cooperative Oncology Group performance status of 0 ( n = 42 ) , 1 ( n = 35 ) , or 2 ( n = 14 ) . OS-6 rate was 62.1 % ( 95 % confidence interval [ CI ] , 48.4 - 74.5 ) with bevacizumab and 73.3 % ( 95 % CI , 54.1 - 87.7 ) with fotemustine . OS-6 rates were lower in bevacizumab-treated patients with MGMT promoter methylated tumors than in those with unmethylated tumors ( 50 % and 85 % , respectively ) , but higher in fotemustine-treated patients ( 87.5 % and 50 % , respectively ) . OS rates at 9 months were 37.9 % ( 95 % CI , 25.5 - 5 
    Output:
    
The use of anti-angiogenic therapy does not significantly improve overall survival in newly diagnosed people with glioblastoma .
Thus , there is insufficient evidence to support the use of anti-angiogenic therapy for people with newly diagnosed glioblastoma at this time .
Overall there is a lack of evidence of a survival advantage for anti-angiogenic therapy over chemotherapy in recurrent glioblastoma .
When considering the combination anti-angiogenic therapy with chemotherapy compared with the same chemotherapy alone , there may possibly be a small improvement in overall survival .
Not addressed here is whether subsets of people with glioblastoma may benefit from anti-angiogenic therapies , nor their utility in other HGG histologies