***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: LBA1010 Background : Taxane-based chemotherapy ( CT ) improves progression-free survival ( PFS ) in patients ( pts ) with newly diagnosed HER2-negative metastatic BC ( MBC ) .  SU , an oral multitargeted tyrosine kinase inhibitor ( MTKI ) , demonstrated antitumor activity in combination with D in a phase I/II study in pts with MBC . A r and omized , open-label , multicenter phase III trial in pts with newly diagnosed ABC tested the hypothesis that addition of a MTKI to D improves PFS vs. D alone . METHODS Eligible pts ( female ; ≥18 yrs ) had an ECOG PS ≤1 , and newly diagnosed HER2-negative MBC or ABC . If (neo)adjuvant therapy included a taxane , relapse must have occurred ≥12 mos after CT . Pts were r and omized ( 1:1 ) to treatment ( tx ) with D 75 mg/m2 iv on day 1 and SU 37.5 mg/day po from day 2 - 15 q3w ( Schedule 2/1 ; Arm A ) , or to D 100 mg/m2 iv 1-hr infusion q3w ( Arm B ) that could be given until progression . If D was discontinued in Arm A for reasons other than progressive disease ( PD ) , single-agent SU 37.5 mg daily was permitted until PD . Median , independently assessed , PFS ( primary endpoint ) was compared between tx arms using stratified and unstratified log-rank tests . Overall objective response rate ( ORR ) , overall survival ( OS ) , pt-reported outcomes , and safety were secondary endpoints . RESULTS As of the data cutoff ( February 1 , 2010 ) , the ITT population comprised 593 pts ( SU+D , n=296 ; D , n=297 ) . The trial did not meet its primary endpoint of prolonging PFS based on the independent radiologic assessment or in prolonging OS . Baseline characteristics were well balanced . Median relative dose intensity ( RDI ) was 94.2 % and 92.4 % for SU+D , and 92.6 % for D arms , respectively . Median PFS was 8.6 mos ( 95 % CI 8.2 - 10.3 ) in the SU+D arm vs 8.3 mos ( 95 % CI 7.7 - 9.6 ) for the D arm ( HR 0.922 ) . Median OS was 24.8 mos ( 95 % CI 21.5 - 33.1 ) in SU+D arm vs 25.5 mos ( 95 % CI 22.8 - 27.8 ) for D arm ( HR 1.207 ) . ORR was significantly better for SU+D ( 51 % ) vs. D ( 39 % ) ( p=0.0018 ) . Frequent all causality grade 3/4 adverse events ( ≥10 % ) were neutropenia ( 46 % ) , h and -foot syndrome ( 17 % ) , and fatigue ( 12 % ) in the SU+D arm and neutropenia ( 44 % ) in the D arm . CONCLUSIONS Based on these data , SU+D is not a recommended treatment option for patients with newly diagnosed ABC . Strategies using antiangiogenic TKIs that increase RR but not OS may need to be revisited . [ Table : see text ] 1006 Background : The addition of bevacizumab ( Bev ) to EC-docetaxel chemotherapy ( CT ) did not improve pathological complete response ( pCR ) rates in unselected patients ( P ) with HER2 negative breast cancers ( von Minckwitz G et al , San Antonio 2010 ) . Secondary aim of GeparQuinto was to determine pCR rates in patients with triple-negative breast cancer ( TNBC ) exclusively . METHODS P with untreated TNBC ( ER and PgR < 10 % and HER2 IHC score 0/1 or FISH negative ; detected locally ) were included in GeparQuinto if they had T1c-T4d tumors and showed no increased cardiac or bleeding risks . P were r and omized to receive 4 cycles EC ( 90/600 mg/m² ) q3w followed by 4 cycles docetaxel ( 100mg/m² ) with or without Bev 15mg/kg q3w added to CT cycles . P not clinical ly responding to EC ± Bev were considered as treatment failures and entered another part of the protocol . P were a stratified subset of the 1948 participants of the HER2 negative part of GeparQuinto . RESULTS In total 684 P with TNBC were r and omized to EC-D ( N=345 ) and EC-D+Bev ( N=339 ) . Median tumor size was 35 / 35 [ -Bev / + Bev ] mm ( clinical ly ) and 28.5 / 28 mm ( sonographically ) ; 15.7 % / 16.0 % had T3 - 4a-d , 1.2 % / 1.5 % bilateral , 13.3 % / 12.7 % multifocal , and 5.8 % / 6.5 % multicentric disease , 97.1 % / 97.9 % had non-lobular , 71.6 % / 69.6 % grade 3 , 57.2 % / 58.0 % node-positive . 32.9 % / 28.7 % discontinued treatment , 20.7 % / 12.3 % due to no response after 4xEC . Additional 4.7 % continued CT but stopped Bev . pCR rate % ( ypT0 , ypN0 ; primary endpoint ) was 27.8 / 36.4 ( p=0.021 ) . Rate of P with ypT0/is was 36.5 / 44.6 ( p=0.04 ) and ypT0/is ypN0 was 32.7 / 40.1 ( p=0.059 ) . If pCRs in non-responding P were included , ypT0,ypN0 rates raised to 28.7 / 38.2 ; ypT0/is ypN0 rates to 33.9 % / 41.9 % . If only P with ER=0 % , PgR=0 % were considered , ypT0 ypN0 was 32.3 % / 40.1 % . Bev treatment ( p=0.013 ) , age ( p=0.021 ) , cT ( p=0.042 ) and grade ( p=0.004 ) were independent predictors for pCR in multivariate logistic regression analysis . Breast conservation was achieved in 75.2 % / 71.5 % ( p=0.39 ) . CONCLUSIONS The effect of Bev on pCR in the GeparQuinto study was restricted exclusively to patients with TNBC . Long term follow-up has to be awaited BACKGROUND E2104 was design ed to evaluate the safety of two different strategies incorporating bevacizumab into anthracycline-containing adjuvant therapy as a precursor to a definitive r and omized phase III trial . PATIENTS AND METHODS Patients were sequentially assigned to one of two treatment arms . In addition to dose-dense doxorubicin and cyclophosphamide followed by paclitaxel ( Taxol ) ( ddAC→T ) , all patients received bevacizumab ( 10 mg/kg every 2 weeks × 26 ) initiated either concurrently with AC ( Arm A : ddBAC→BT→B ) or with paclitaxel ( Arm B : ddAC→BT→B ) . The primary end point was incidence of clinical ly apparent cardiac dysfunction ( CHF ) . RESULTS Patients enrolled were 226 in number ( Arm A 104 , Arm B 122 ) . Grade 3 hypertension , thrombosis , proteinuria and hemorrhage were reported for 12 , 2 , 2 and < 1 % of patients , respectively . Two patients developed grade 3 or more cerebrovascular ischemia . Three patients in each arm developed CHF . There was no significant difference between arms in the proportion of patients with an absolute decrease in left ventricular ejection fraction of > 15 % or > 10 % to below the lower limit of normal post AC or post bevacizumab . CONCLUSIONS Incorporation of bevacizumab into anthracycline-containing adjuvant therapy does not result in prohibitive cardiac toxicity . The definitive phase III trial ( E5103 ) was activated with systematic and extensive cardiac monitoring to define the true impact of bevacizumab on cardiac function PURPOSE No biomarkers have been identified to predict outcome with the use of an antiangiogenesis agent for cancer . Vascular endothelial growth factor ( VEGF ) genetic variability has been associated with altered risk of breast cancer and variable promoter activity . Therefore , we evaluated the association of VEGF genotype with efficacy and toxicity in E2100 , a phase III study comparing paclitaxel versus paclitaxel plus bevacizumab as initial chemotherapy for metastatic breast cancer . PATIENTS AND METHODS DNA was extracted from tumor blocks of patients from E2100 . Three hundred sixty-three sample s were available to evaluate associations between genotype and outcome . Genotyping was performed for selected polymorphisms in VEGF and VEGF receptor 2 . Testing for associations between each polymorphism and efficacy and toxicity was performed . RESULTS The VEGF-2578 AA genotype was associated with a superior median overall survival ( OS ) in the combination arm when compared with the alternate genotypes combined ( hazard ratio = 0.58 ; 95 % CI , 0.36 to 0.93 ; P = .023 ) . The VEGF-1154 A allele also demonstrated a superior median OS with an additive effect of each active allele in the combination arm but not the control arm ( hazard ratio = 0.62 ; 95 % CI , 0.46 to 0.83 ; P = .001 ) . Two additional genotypes , VEGF-634 CC and VEGF-1498 TT , were associated with significantly less grade 3 or 4 hypertension in the combination arm when compared with the alternate genotypes combined ( P = .005 and P = .022 , respectively ) . CONCLUSION Our data support an association between VEGF genotype and median OS as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer BACKGROUND Bevacizumab , a monoclonal antibody against vascular endothelial growth factor , has been shown to benefit patients with a variety of cancers . METHODS Between July 2001 and April 2004 , the Eastern Cooperative Oncology Group ( ECOG ) conducted a r and omized study in which 878 patients with recurrent or advanced non-small-cell lung cancer ( stage IIIB or IV ) were assigned to chemotherapy with paclitaxel and carboplatin alone ( 444 ) or paclitaxel and carboplatin plus bevacizumab ( 434 ) . Chemotherapy was administered every 3 weeks for six cycles , and bevacizumab was administered every 3 weeks until disease progression was evident or toxic effects were intolerable . Patients with squamous-cell tumors , brain metastases , clinical ly significant hemoptysis , or inadequate organ function or performance status ( ECOG performance status , > 1 ) were excluded . The primary end point was overall survival . RESULTS The median survival was 12.3 months in the group assigned to chemotherapy plus bevacizumab , as compared with 10.3 months in the chemotherapy-alone group ( hazard ratio for death , 0.79 ; P=0.003 ) . The median progression-free survival in the two groups was 6.2 and 4.5 months , respectively ( hazard ratio for disease progression , 0.66 ; P<0.001 ) , with corresponding response rates of 35 % and 15 % ( P<0.001 ) . Rates of clinical ly significant bleeding were 4.4 % and 0.7 % , respectively ( P<0.001 ) . There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group , including 5 from pulmonary hemorrhage . CONCLUSIONS The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non-small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths . ( Clinical Trials.gov number , NCT00021060 . LBA1011 Background : Recent trials support combining an antiangiogenic agent with chemotherapy ( CT ) in pretreated patients ( pts ) with metastatic BC ( MBC ) .  SU , an oral multitargeted tyrosine kinase inhibitor demonstrated single-agent activity ( 11 % ORR ) in heavily pretreated pts with MBC . Antitumor activity with SU+C was reported in pts with advanced solid tumors . This multicenter , r and omized , phase III trial ( SUN 1099 ) compared the efficacy and safety of SU + C vs. C in pts with ABC . METHODS Eligibility criteria were : age ≥18 yrs , ECOG PS ≤1 , measurable HER2-positive ( FISH+ , CISH+ or IHC3 + ) or -negative ABC , no brain metastases , prior treatment ( tx ) with an anthracycline and taxane in the (neo)adjuvant or metastatic setting , and ≤2 
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RESULTS AND DISCUSSION Phase III trials in advanced BC have demonstrated a reduction in the risk of disease progression ( 22 - 52 % ) , improved response rates and net improvements in progression-free survival of 1.2 to 5.5 months , but no significant improvements in overall survival with the addition of bevacizumab to chemotherapy .
Bevacizumab-containing regimens have also been associated with higher overall adverse event rates compared to chemotherapy alone .
Phase III trials of the tyrosine kinase inhibitor sunitinib were negative , while r and omized phase II trials of sorafenib and pazopanib have improved some outcomes when combined with chemotherapy or targeted therapy compared to controls .
In addition to expected vascular class safety signals , tyrosine kinase inhibitors show " off-target " side effects .
Ongoing clinical trials evaluating combinatorial strategies based on biological synergies and translational studies identifying biological predictors of response will be crucial to establish meaningful clinical benefits in selected BC population s. CONCLUSION Most trials of anti-angiogenic agents in BC have reported improved response rate and progression-free survival but no increase in overall survival compared to chemotherapy alone .