***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: PURPOSE Open-label , phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer . PATIENTS AND METHODS Patients were stratified and r and omly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day . Primary end point was overall survival ( OS ) . RESULTS Early trial termination occurred for futility and safety reasons . A total of 1,074 patients were r and omly assigned to the study ( sunitinib arm , n = 530 ; sorafenib arm , n = 544 ) . For sunitinib and sorafenib , respectively , median OS was 7.9 versus 10.2 months ( hazard ratio [ HR ] , 1.30 ; one-sided P = .9990 ; two-sided P = .0014 ) ; median progression-free survival ( PFS ; 3.6 v 3.0 months ; HR , 1.13 ; one-sided P = .8785 ; two-sided P = .2286 ) and time to progression ( TTP ; 4.1 v 3.8 months ; HR , 1.13 ; one-sided P = .8312 ; two-sided P = .3082 ) were comparable . Median OS was similar among Asian ( 7.7 v 8.8 months ; HR , 1.21 ; one-sided P = .9829 ) and hepatitis B-infected patients ( 7.6 v 8.0 months ; HR , 1.10 ; one-sided P = .8286 ) , but was shorter with sunitinib in hepatitis C-infected patients ( 9.2 v 17.6 months ; HR , 1.52 ; one-sided P = .9835 ) . Sunitinib was associated with more frequent and severe adverse events ( AEs ) than sorafenib . Common grade 3/4 AEs were thrombocytopenia ( 29.7 % ) and neutropenia ( 25.7 % ) for sunitinib ; h and -foot syndrome ( 21.2 % ) for sorafenib . Discontinuations owing to AEs were similar ( sunitinib , 13.3 % ; sorafenib , 12.7 % ) . CONCLUSION OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib . OS was comparable in Asian and hepatitis B-infected patients . OS was superior in hepatitis C-infected patients who received sorafenib . Sunitinib-treated patients reported more frequent and severe toxicity PURPOSE To investigate whether sunitinib plus docetaxel improves clinical outcomes for patients with human epidermal growth factor receptor 2 (HER2)/neu-negative advanced breast cancer ( ABC ) versus docetaxel alone . PATIENTS AND METHODS In this phase III study , patients were r and omly assigned to open-label combination therapy ( sunitinib 37.5 mg/d , days 2 to 15 every 3 weeks ; and docetaxel 75 mg/m(2 ) , day 1 every 3 weeks ) or monotherapy ( docetaxel 100 mg/m(2 ) every 3 weeks ) .  Progression-free survival ( PFS )  was the primary end point . RESULTS Two hundred ninety-six patients were r and omly assigned to combination therapy , and 297 patients were assigned to monotherapy .  Median PFS times were 8.6 and 8.3 months with combination therapy and monotherapy , respectively ( hazard ratio , 0.92 ; one-sided P = .265 ) . The objective response rate ( ORR ) was significantly higher with the combination ( 55 % ) than with monotherapy ( 42 % ; one-sided P = .001 ) . Duration of response was similar in both arms ( 7.5 months with the combination v 7.2 months with monotherapy ) . Median overall survival ( OS ) times were 24.8 and 25.5 months with combination therapy and monotherapy , respectively ( one-sided P = .904 ) . There were 107 deaths with the combination and 91 deaths with monotherapy . The frequency of common adverse events ( AEs ) was higher with the combination , as were treatment discontinuations caused by AEs . CONCLUSION The combination of sunitinib plus docetaxel improved ORR but did not prolong either PFS or OS compared with docetaxel alone when given to an unselected HER2/neu-negative cohort as first-line treatment for ABC . Sunitinib combination therapy may also have result ed in AEs that yield an unfavorable risk-benefit ratio . The sunitinib-docetaxel regimen evaluated in this study is not recommended for further use in ABC PURPOSE This phase II/III double-blind study assessed efficacy and safety of cediranib with st and ard chemotherapy as initial therapy for advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Paclitaxel ( 200 mg/m(2 ) ) and carboplatin ( area under the serum concentration-time curve 6 ) were given every 3 weeks , with daily oral cediranib or placebo at 30 mg ( first 45 patients received 45 mg ) . Progression-free survival ( PFS ) was the primary outcome of the phase II interim analysis ; phase III would proceed if the hazard ratio ( HR ) for PFS < or = 0.77 and toxicity were acceptable . Results A total of 296 patients were enrolled , 251 to the 30-mg cohort . The phase II interim analysis demonstrated a significantly higher response rate ( RR ) for cediranib than for placebo , HR of 0.77 for PFS , no excess hemoptysis , and a similar number of deaths in each arm . The study was halted to review imbalances in assigned causes of death . In the primary phase II analysis ( 30-mg cohort ) , the adjusted HR for PFS was 0.77 ( 95 % CI , 0.56 to 1.08 ) with a higher RR for cediranib than for placebo ( 38 % v 16 % ; P < .0001 ) . Cediranib patients had more hypertension , hypothyroidism , h and -foot syndrome , and GI toxicity . Hypoalbuminemia , age > or = 65 years , and female sex predicted increased toxicity . Survival up date ( N = 296 ) 10 months after study unblinding favored cediranib over placebo ( median of 10.5 months v 10.1 months ; HR , 0.78 ; 95 % CI , 0.57 to 1.06 ; P = .11 ) . Causes of death in the cediranib 30-mg cohort were NSCLC ( 81 % ) , protocol toxicity + /- NSCLC ( 13 % ) , and other ( 6 % ) ; for the placebo group , they were 98 % , 0 % , and 2 % , respectively . CONCLUSION The addition of cediranib to carboplatin/paclitaxel results in improved response and PFS , but does not appear tolerable at a 30-mg dose . Consequently , the National Cancer Institute of Canada Clinical Trials Group and the Australasian Lung Cancer Trials Group initiated a r and omized , double-blind , placebo-controlled trial of cediranib 20 mg with carboplatin and paclitaxel in advanced NSCLC BACKGROUND Cediranib is a highly potent vascular endothelial growth factor ( VEGF ) signalling inhibitor with activity against VEGF receptors 1 , 2 and 3 . This Phase II , r and omised , double-blind , parallel-group study compared the efficacy of cediranib with placebo in patients with metastatic or recurrent clear cell renal cell carcinoma who had not previously received a VEGF signalling inhibitor . METHODS Patients were r and omised ( 3:1 ) to cediranib 45 mg/day or placebo .  The primary objective was comparison of change from baseline in tumour size after 12 weeks of therapy . Secondary objectives included response rate and duration , progression-free survival ( PFS ) and safety and tolerability . Patients in the placebo group could cross over to open-label cediranib at 12 weeks or earlier if their disease had progressed . This study has been completed and is registered with Clinical Trials.gov , number NCT00423332 . FINDINGS Patients ( n=71 ) were r and omised to receive cediranib ( n=53 ) or placebo ( n=18 ) . The primary study outcome revealed that , after 12weeks of therapy , there was a significant difference in mean percentage change from baseline in tumour size between the cediranib ( -20 % ) and placebo ( + 20 % ) arms ( p<0.0001 ) . Eighteen patients ( 34 % ) on cediranib achieved a partial response and 25 ( 47 % ) experienced stable disease .  Cediranib treatment prolonged PFS significantly compared with placebo ( hazard ratio (HR)=0.45 , 90%confidence interval : 0.26 - 0.76 , p=0.017 ; median PFS 12.1 versus 2.8 months ) . The most common adverse events in patients receiving cediranib were diarrhoea ( 74 % ) , hypertension ( 64 % ) , fatigue ( 58 % ) and dysphonia ( 58 % ) . INTERPRETATION Cediranib monotherapy demonstrated significant evidence of antitumour activity in patients with advanced renal cell carcinoma . The adverse event profile was consistent with previous studies of cediranib 45 mg PURPOSE To compare the efficacy of cediranib ( a vascular endothelial growth factor receptor tyrosine kinase inhibitor [ VEGFR TKI ] ) with that of bevacizumab ( anti-VEGF-A monoclonal antibody ) in combination with chemotherapy as first-line treatment for advanced metastatic colorectal cancer ( mCRC ) . PATIENTS AND METHODS HORIZON III [ Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer ] had an adaptive phase II/III design . Patients r and omly assigned 1:1:1 received mFOLFOX6 [ oxaliplatin 85 mg/m(2 ) and leucovorin 400 mg/m(2 ) intravenously followed by fluorouracil 400 mg/m(2 ) intravenously on day 1 and then continuous infusion of 2,400 mg/m(2 ) over the next 46 hours every 2 weeks ] with cediranib ( 20 or 30 mg per day ) or bevacizumab ( 5 mg/kg every 14 days ) . An independent end-of-phase II analysis concluded that mFOLFOX6/cediranib 20 mg met predefined criteria for continuation ; subsequent patients received mFOLFOX6/cediranib 20 mg or mFOLFOX6/bevacizumab ( r and omly assigned 1:1 ) . The primary objective was to compare progression-free survival ( PFS ) . RESULTS In all , 1,422 patients received mFOLFOX6/cediranib  20 mg ( n = 709 ) or mFOLFOX6/bevacizumab ( n = 713 ) . Primary analysis revealed no significant difference between arms for PFS ( hazard ratio [ HR ] , 1.10 ; 95 % CI , 0.97 to 1.25 ; P = .119 ) , overall survival ( OS ; HR , 0.95 ; 95 % CI , 0.82 to 1.10 ; P = .541 ) , or overall response rate ( 46.3 % v 47.3 % ) . Median PFS and OS were 9.9 and 22.8 months for mFOLFOX6/cediranib and 10.3 and 21.3 months for mFOLFOX6/bevacizumab . The PFS upper 95 % CI was outside the predefined noninferiority limit ( HR < 1.2 ) . Common adverse events with more than 5 % incidence in the cediranib arm included diarrhea , neutropenia , and hypertension .  Cediranib-treated patients completed fewer chemotherapy cycles than bevacizumab-treated patients ( median 10 v 12 cycles ) . Patient-reported outcomes ( PROs ) were significantly less favorable in cediranib-treated versus bevacizumab-treated patients ( P < .001 ) . CONCLUSION Cediranib activity , in terms of PFS and OS , was comparable to that of bevacizumab when added to mFOLFOX6 ; however , the predefined boundary for PFS noninferiority was not met . The cediranib  safety profile was consistent with previous studies but led to less favorable PROs compared with bevacizumab . Investigation of oral TKIs in CRC continues BACKGROUND Axitinib is a potent , selective inhibitor of vascular endothelial growth factor ( VEGF ) receptors 1 , 2 , and 3 . A r and omised phase 2 trial of gemcitabine with or without axitinib in advanced pancreatic cancer suggested increased overall survival in axitinib-treated patients . On the basis of these results , we aim ed to assess the 
    Output:
    
Our meta- analysis has demonstrated that sunitinib , axitinib , cediranib and regorafenib are associated with a higher risk of developing all grade and high grade hypertension compared with control .
While for bleeding , only the sunitinib subgroup RR was significant compared to axitinib or cediranib .