***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 
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    ***EXAMPLES*** 
    Input: PURPOSE This r and omized , open-label phase II study compared the efficacy of sunitinib monotherapy with that of single-agent st and ard-of-care ( SOC ) chemotherapy in patients with previously treated advanced triple-negative breast cancer ( TNBC ) . METHODS Patients with advanced TNBC , relapsed after anthracycline- and taxane-based chemotherapy  , were r and omized to receive either sunitinib ( 37.5 mg/day ) or the investigator 's choice of SOC therapy .  Progression-free survival was the primary endpoint . RESULTS Median progression-free survival was 2.0 months with sunitinib and 2.7 months with SOC chemotherapy ( one-sided P = 0.888 ) . Median overall survival was not prolonged with sunitinib ( 9.4 months ) compared with SOC chemotherapy ( 10.5 months ; one-sided P = 0.839 ) . The objective response rate was 3 % with sunitinib and 7 % with SOC chemotherapy ( one-sided P = 0.962 ) . CONCLUSIONS Sunitinib monotherapy did not improve efficacy compared with SOC chemotherapy in patients with previously treated advanced TNBC , for which identification of effective treatments and therapeutic targets remains an urgent need . TRIAL REGISTRATION NCT00246571 BACKGROUND Bevacizumab and the antimetabolites capecitabine and gemcitabine have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer . The primary aims of this trial were to determine whether the addition of capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel , followed by doxorubicin plus cyclophosphamide , would increase the rates of pathological complete response in the breast in women with operable , human epidermal growth factor receptor 2 (HER2)-negative breast cancer and whether adding bevacizumab to these chemotherapy regimens would increase the rates of pathological complete response . METHODS We r and omly assigned 1206 patients to receive neoadjuvant therapy consisting of docetaxel ( 100 mg per square meter of body-surface area on day 1 ) , docetaxel ( 75 mg per square meter on day 1 ) plus capecitabine ( 825 mg per square meter twice a day on days 1 to 14 ) , or docetaxel ( 75 mg per square meter on day 1 ) plus gemcitabine ( 1000 mg per square meter on days 1 and 8) for four cycles , with all regimens followed by treatment with doxorubicin-cyclophosphamide for four cycles . Patients were also r and omly assigned to receive or not to receive bevacizumab ( 15 mg per kilogram of body weight ) for the first six cycles of chemotherapy . RESULTS The addition of capecitabine or gemcitabine to docetaxel therapy , as compared with docetaxel therapy alone , did not significantly increase the rate of pathological complete response ( 29.7 % and 31.8 % , respectively , vs. 32.7 % ; P=0.69 ) . Both capecitabine and gemcitabine were associated with increased toxic effects -- specifically , the h and -foot syndrome , mucositis , and neutropenia . The addition of bevacizumab significantly increased the rate of pathological complete response ( 28.2 % without bevacizumab vs. 34.5 % with bevacizumab , P=0.02 ) . The effect of bevacizumab on the rate of pathological complete response was not the same in the hormone-receptor-positive and hormone-receptor-negative subgroups . The addition of bevacizumab increased the rates of hypertension , left ventricular systolic dysfunction , the h and -foot syndrome , and mucositis . CONCLUSIONS The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response , which was the primary end point of this study . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT00408408 . ) BACKGROUND The addition of bevacizumab to chemotherapy improves progression-free survival in metastatic breast cancer and pathological complete response rates in the neoadjuvant setting . Micrometastases are dependent on angiogenesis , suggesting that patients might benefit from anti-angiogenic strategies in the adjuvant setting . We therefore assessed the addition of bevacizumab to chemotherapy in the adjuvant setting for women with triple-negative breast cancer . METHODS For this open-label , r and omised phase 3 trial we recruited patients with central ly confirmed triple-negative operable primary invasive breast cancer from 360 sites in 37 countries . We r and omly allocated patients aged 18 years or older ( 1:1 with block r and omisation ; stratified by nodal status , chemotherapy  [ with an anthracycline , taxane , or both ] , hormone receptor status [ negative vs low ] , and type of surgery ) to receive a minimum of four cycles of chemotherapy either alone or with bevacizumab ( equivalent of 5 mg/kg every week for 1 year ) . The primary endpoint was invasive disease-free survival ( IDFS ) . Efficacy analyses were based on the intention-to-treat population , safety analyses were done on all patients who received at least one dose of study drug , and plasma biomarker analyses were done on all treated patients consenting to biomarker analyses and providing a measurable baseline plasma sample . This trial is registered with Clinical Trials.gov , number NCT00528567 . FINDINGS Between Dec 3 , 2007 , and March 8 , 2010 , we r and omly assigned 1290 patients to receive chemotherapy alone  and 1301 to receive bevacizumab plus chemotherapy . Most patients received anthracycline-containing therapy ; 1638 ( 63 % ) of the 2591 patients had node-negative disease . At the time of analysis of IDFS , median follow-up was 31·5 months ( IQR 25·6 - 36·8 ) in the chemotherapy-alone group and 32·0 months ( 27·5 - 36·9 ) in the bevacizumab group . At the time of the primary analysis , IDFS events had been reported in 205 patients ( 16 % ) in the chemotherapy-alone group and in 188 patients ( 14 % ) in the bevacizumab group ( hazard ratio [ HR ] in stratified log-rank analysis 0·87 , 95 % CI 0·72 - 1·07 ; p=0·18 ) . 3-year IDFS was 82·7 % ( 95 % CI 80·5 - 85·0 ) with chemotherapy alone and 83·7 % ( 81·4 - 86·0 ) with bevacizumab and chemotherapy . After 200 deaths , no difference in overall survival was noted between the groups ( HR 0·84 , 95 % CI 0·64 - 1·12 ; p=0·23 ) . Exploratory biomarker assessment suggests that patients with high pre-treatment plasma VEGFR-2 might benefit from the addition of bevacizumab ( Cox interaction test p=0·029 ) . Use of bevacizumab versus chemotherapy alone was associated with increased incidences of grade 3 or worse hypertension ( 154 patients [ 12 % ] vs eight patients [ 1 % ] ) , severe cardiac events occurring at any point during the 18-month safety reporting period ( 19 [ 1 % ] vs two [ < 0·5 % ] ) , and treatment discontinuation ( bevacizumab , chemotherapy , or both ; 256 [ 20 % ] vs 30 [ 2 % ] ) ; we recorded no increase in fatal adverse  events with bevacizumab ( four [ < 0·5 % ] vs three [ < 0·5 % ] ) . INTERPRETATION Bevacizumab can not be recommended as adjuvant treatment in unselected patients with triple-negative breast cancer . Further follow-up is needed to assess the potential effect of bevacizumab  on overall survival Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists INTRODUCTION A multicenter , open-label phase III study was conducted to test whether sunitinib plus paclitaxel prolongs progression-free survival ( PFS ) compared with bevacizumab plus paclitaxel as first-line treatment for patients with HER2(- ) advanced breast cancer . PATIENTS AND METHODS Patients with HER2(- ) advanced breast cancer who were disease free for ≥ 12 months after adjuvant taxane treatment were r and omized ( 1:1 ; planned enrollment 740 patients ) to receive  intravenous  ( I.V. ) paclitaxel 90 mg/m(2 ) every week for 3 weeks in 4-week cycles plus either sunitinib 25 to 37.5 mg every day or bevacizumab 10 mg/kg I.V. every 2 weeks . [ corrected ] RESULTS The trial was terminated early because of futility in reaching the primary endpoint as determined by the independent data monitoring committee during an interim futility analysis . At data cutoff , 242 patients had been r and omized to sunitinib-paclitaxel and 243 patients to bevacizumab-paclitaxel  . Median PFS was shorter with sunitinib-paclitaxel ( 7.4 vs. 9.2 months ; hazard ratio [ HR ] 1.63 [ 95 % confidence interval ( CI ) , 1.18 - 2.25 ] ; 1-sided P = .999 ) . At a median follow-up of 8.1 months , with 79 % of sunitinib-paclitaxel and 87 % of bevacizumab-paclitaxel  patients alive , overall survival analysis favored bevacizumab-paclitaxel ( HR 1.82 [ 95 % CI , 1.16 - 2.86 ] ; 1-sided P = .996 ) . The objective response rate was 32 % in both arms , but median duration of response was shorter with sunitinib-paclitaxel ( 6.3 vs. 14.8 months ) . Bevacizumab-paclitaxel was better tolerated than sunitinib-paclitaxel . This was primarily due to a high frequency of grade 3/4 , treatment-related neutropenia  with sunitinib-paclitaxel ( 52 % ) precluding delivery of the prescribed doses of both drugs . CONCLUSION The sunitinib-paclitaxel regimen evaluated in this study was clinical ly inferior to the bevacizumab-paclitaxel regimen and is not a recommended treatment option for patients with advanced breast cancer In February 2008 , the U.S. Food and Drug Administration ( FDA ) granted accelerated approval to bevacizumab ( Avastin ) in combination with paclitaxel as first-line treatment for HER-2 negative metastatic breast cancer . Approval was based on the results of E2100 , a cooperative-group r and omized trial that showed a 5.5-month increase in progression-free survival associated with the addition of bevacizumab to paclitaxel therapy.1,2 Confirmatory studies by Genentech , the manufacturer , however , showed that bevacizumab 's benefits for progression-free survival may be appreciably smaller than those shown in E2100 and have demonstrated convincingly that the addition of bevacizumab to the chemotherapy agents they have tested offers no . . PURPOSE The AVAGAST study showed that adding bevacizumab to chemotherapy in patients with advanced gastric cancer improves progression-free survival and tumor response rate but not overall survival . To examine the hypothesis that angiogenic markers may have predictive value for bevacizumab  efficacy in gastric cancer , AVAGAST included a prospect i ve , m and atory biomarker program . PATIENTS AND METHODS Patients with previously untreated , locally advanced or metastatic gastric cancer were r and omly assigned to  bevacizumab ( n = 387 )  or placebo ( n = 387 ) in combination with chemotherapy . Blood and tumor tissue sample s were collected at baseline . Prespecified biomarkers included plasma vascular endothelial growth factor-A ( VEGF-A ) , protein expression of neuropilin-1 , and VEGF recept 
    Output:
    
VEGF-A level is a reasonable c and i date biomarker for bevacizumab in the treatment of breast cancer .