***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 This trial evaluated the efficacy and safety of sorafenib plus gemcitabine/cisplatin in chemotherapy-naive patients with unresectable stage IIIB to IV nonsquamous non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Between February 2007 and March 2009 , 904 patients were r and omly assigned to daily sorafenib ( 400 mg twice a day ) or matching placebo plus gemcitabine ( 1,250 mg/m(2 ) per day on days 1 and 8) and cisplatin ( 75 mg/m(2 ) on day 1 ) for up to six 21-day cycles . Because of safety findings from the Evaluation of Sorafenib , Carboplatin and Paclitaxel Efficacy in NSCLC ( ESCAPE ) trial , patients with squamous cell histology were withdrawn from the trial in February 2008 and excluded from analysis . The primary end point was overall survival ( OS ) , and secondary end points included progression-free survival ( PFS ) and time-to-progression ( TTP ) . RESULTS The primary analysis population consisted of 772 patients ( sorafenib , 385 ; placebo , 387 ) ; the two groups had similar demographic and baseline characteristics . Median OS was similar in the sorafenib and placebo groups ( 12.4 v 12.5 months ; hazard ratio [ HR ] , 0.98 ; P = .401 ) . By investigator assessment , sorafenib improved median PFS ( 6.0 v 5.5 months ; HR , 0.83 ; P = .008 ) and TTP ( 6.1 v 5.5 months ; HR , 0.73 ; P < .001 ) . Grade 3 to 4 drug-related adverse events more than two-fold higher in the sorafenib group included h and -foot skin reaction ( 8.6 % v 0.3 % ) , fatigue ( 7.3 % v 3.6 % ) , rash ( 5.7 % v 0.5 % ) , and hypertension ( 4.2 % v 1.8 % ) . No unexpected toxicities were observed . CONCLUSION This study did not meet its primary end point of improved OS when sorafenib was added to first-line gemcitabine/cisplatin in patients with advanced nonsquamous NSCLC . Identification of predictive biomarkers is warranted in future trials of sorafenib Purpose : Hypertension is a commonly reported side effect in antiangiogenic therapy . We investigated the hypothesis that telatinib , a small molecule angiogenesis inhibitor , impairs vascular function , induces rarefaction , and causes hypertension . Experimental Design : A side- study was done in a phase I trial of telatinib , a small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptors 2 and 3 , platelet-derived growth factor receptor , and c-KIT in patients with advanced solid tumors . Measurements of blood pressure , flow-mediated dilation , nitroglycerin-mediated dilation , aortic pulse wave velocity , skin blood flux with laser Doppler flow , and capillary density with sidestream dark field imaging were done at baseline and after 5 weeks of treatment . Blood pressure and proteinuria were measured weekly . Results : Mean systolic and diastolic blood pressure values increased significantly at + 6.6 mm Hg ( P = 0.009 ) and + 4.7 mm Hg ( P = 0.016 ) , respectively . Mean flow-mediated dilation and mean nitroglycerin-mediated dilation values significantly decreased by −2.1 % ( P = 0.003 ) and −5.1 % ( P = 0.001 ) , respectively . After 5 weeks of treatment , mean pulse wave velocity significantly increased by 1.2 m/s ( P = 0.001 ) . A statistically significant reduction of mean skin blood flux of 532.8 % arbitrary units was seen ( P = 0.015 ) . Capillary density statistically significantly decreased from 20.8 to 16.7 capillary loops ( P = 0.015 ) . Proteinuria developed or increased in six patients during telatinib treatment . Conclusion : The increase in blood pressure observed in the treatment with telatinib , an angiogenesis inhibitor , may be caused by functional or structural rarefaction BACKGROUND Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2 . We aim ed to assess efficacy and safety of treatment with docetaxel plus ramucirumab or placebo as second-line treatment for patients with stage IV non-small-cell-lung cancer ( NSCLC ) after platinum-based therapy . METHODS In this multicentre , double-blind , r and omised phase 3 trial ( REVEL ) , we enrolled patients with squamous or non-squamous NSCLC who had progressed during or after a first-line platinum-based chemotherapy regimen . Patients were r and omly allocated ( 1:1 ) with a central ised , interactive voice-response system ( stratified by sex , region , performance status , and previous maintenance therapy [ yes vs no ] ) to receive docetaxel 75 mg/m(2 ) and either ramucirumab ( 10 mg/kg ) or placebo on day 1 of a 21 day cycle until disease progression , unacceptable toxicity , withdrawal , or death . The primary endpoint was overall survival in all patients allocated to treatment . We assessed adverse events according to treatment received . This study is registered with Clinical Trials.gov , number NCT01168973 . FINDINGS Between Dec 3 , 2010 , and Jan 24 , 2013 , we screened 1825 patients , of whom 1253 patients were r and omly allocated to treatment . Median overall survival was 10·5 months ( IQR 5·1 - 21·2 ) for 628 patients allocated ramucirumab plus docetaxel and 9·1 months ( 4·2 - 18·0 ) for 625 patients who received placebo plus docetaxel ( hazard ratio 0·86 , 95 % CI 0·75 - 0·98 ; p=0·023 ) . Median progression-free survival was 4·5 months ( IQR 2·3 - 8·3 ) for the ramucirumab group compared with 3·0 months ( 1·4 - 6·9 ) for the control group ( 0·76 , 0·68 - 0·86 ; p<0·0001 ) . We noted treatment-emergent adverse events in 613 ( 98 % ) of 627 patients in the ramucirumab safety population and 594 ( 95 % ) of 618 patients in the control safety population . The most common grade 3 or worse adverse events were neutropenia ( 306 patients [ 49 % ] in the ramucirumab group vs 246 [ 40 % ] in the control group ) , febrile neutropenia ( 100 [ 16 % ] vs 62 [ 10 % ] ) , fatigue ( 88 [ 14 % ] vs 65 [ 10 % ] ) , leucopenia ( 86 [ 14 % ] vs 77 [ 12 % ] ) , and hypertension ( 35 [ 6 % ] vs 13 [ 2 % ] ) . The numbers of deaths from adverse events ( 31 [ 5 % ] vs 35 [ 6 % ] ) and grade 3 or worse pulmonary haemorrhage ( eight [ 1 % ] vs eight [ 1 % ] ) did not differ between groups . Toxicities were manageable with appropriate dose reductions and supportive care . INTERPRETATION Ramucirumab plus docetaxel improves survival as second-line treatment of patients with stage IV NSCLC . FUNDING Eli Lilly 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 PURPOSE V and etanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor ( VEGFR ) and epidermal growth factor receptor ( EGFR ) signaling . In this two-part phase II study , the efficacy and safety of v and etanib was compared with that of gefitinib , an inhibitor of EGFR signaling . PATIENTS AND METHODS Patients ( N = 168 ) with locally advanced or metastatic ( stage IIIB/IV ) non-small-cell lung cancer ( NSCLC ) , after failure of first-line with or without second-line platinum-based chemotherapy  , received once-daily v and etanib 300 mg ( n = 83 ) or gefitinib 250 mg ( n = 85 ) until disease progression or evidence of toxicity ( part A ) . After a 4-week washout period , eligible patients had the option to switch to the alternative treatment ( part B ) . Progression-free survival ( PFS ) was the primary efficacy assessment in part A , which was design ed to have a higher than 75 % power to detect a 33 % prolongation of PFS at a one-sided significance level of .2 . RESULTS In part A , v and etanib  prolonged PFS compared with gefitinib ( hazard ratio = 0.69 ; 95 % CI , 0.50 to 0.96 ; one-sided P = .013 ) . Patients receiving v and etanib experienced adverse events that were manageable and generally consistent with inhibition of EGFR and VEGFR signaling , including diarrhea , rash , and hypertension . There were no unexpected safety findings with gefitinib . Overall survival , a secondary assessment , was not significantly different between patients initially r and omly assigned to either v and etanib or gefitinib . CONCLUSION The primary efficacy objective was achieved , with v and etanib demonstrating a significant prolongation of PFS versus gefitinib . V and etanib 300 mg/d is currently being evaluated as a monotherapy in two r and omized phase III studies in advanced NSCLC BACKGROUND Bevacizumab and erlotinib target different tumour growth pathways with little overlap in their toxic-effect profiles . On the basis of promising results from a phase 1/2 trial assessing safety and activity of erlotinib plus bevacizumab for recurrent or refractory non-small-cell lung cancer ( NSCLC ) , we aim ed to assess efficacy and safety of this combination in a phase 3 trial . METHODS In our double-blind , placebo-controlled , r and omised phase 3 trial ( BeTa ) , we enrolled patients with recurrent or refractory NSCLC who presented to 177 study sites in 12 countries after failure of first-line treatment . Patients were r and omly allocated in a one-to-one ratio to receive erlotinib plus bevacizumab ( bevacizumab group ) or erlotinib plus placebo ( control group ) according to a computer-generated r and omisation sequence by use of an interactive voice response system 
    Output:
    
The AEs associated with angiogenesis inhibitors were generally predictable and manageable .
Conclusion Angiogenesis inhibitors were superior to non-angiogenesis inhibitors in terms of ORR , DCR , PFS and OS in advanced NSCLC patients .