***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 VEGFR-2 has a role in gastric cancer pathogenesis and progression . We assessed whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , in combination with paclitaxel would increase overall survival in patients previously treated for advanced gastric cancer compared with  placebo plus paclitaxel . METHODS This r and omised , placebo-controlled , double-blind , phase 3 trial was done at 170 centres in 27 countries in North and South America , Europe , Asia , and Australia . Patients aged 18 years or older with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy ( platinum plus fluoropyrimidine with or without an anthracycline )  were r and omly assigned with a central ised interactive voice or web-response system in a 1:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 , plus paclitaxel 80 mg/m(2 ) intravenously on days 1 , 8 , and 15 of a 28-day cycle . A permuted block r and omisation , stratified by geographic region , time to progression on first-line therapy , and disease measurability , was used . The primary endpoint was overall survival . Efficacy analysis was by intention to treat , and safety analysis included all patients who received at least one treatment with study drug . This trial is registered with Clinical Trials.gov , number NCT01170663 , and has been completed ; patients who are still receiving treatment are in the extension phase . FINDINGS Between Dec 23 , 2010 , and Sept 23 , 2012 , 665 patients were r and omly assigned to treatment-330 to ramucirumab plus paclitaxel and 335 to placebo plus paclitaxel . Overall survival was significantly longer in the ramucirumab plus paclitaxel group than in the placebo plus paclitaxel group ( median 9·6 months [ 95 % CI 8·5 - 10·8 ] vs 7·4 months [ 95 % CI 6·3 - 8·4 ] , hazard ratio 0·807 [ 95 % CI 0·678 - 0·962 ] ; p=0·017 ) . Grade 3 or higher adverse events that occurred in more than 5 % of patients in the ramucirumab plus paclitaxel group versus placebo plus paclitaxel  included neutropenia ( 133 [ 41 % ] of 327 vs 62 [ 19 % ] of 329 ) , leucopenia ( 57 [ 17 % ] vs 22 [ 7 % ] ) , hypertension ( 46 [ 14 % ] vs eight [ 2 % ] ) , fatigue ( 39 [ 12 % ] vs 18 [ 5 % ] ) , anaemia ( 30 [ 9 % ] vs 34 [ 10 % ] ) , and abdominal pain ( 20 [ 6 % ] vs 11 [ 3 % ] ) . The incidence of grade 3 or higher febrile neutropenia was low in both groups ( ten [ 3 % ] vs eight [ 2 % ] ) . INTERPRETATION The combination of ramucirumab with paclitaxel significantly increases overall survival compared with placebo plus paclitaxel , and could be regarded as a new st and ard second-line treatment for patients with advanced gastric cancer . FUNDING Eli Lilly and Company OBJECTIVE Vascular endothelial growth factor ( VEGF ) receptor-mediated signaling contributes to ovarian cancer pathogenesis . Elevated VEGF expression is associated with poor clinical outcomes . We investigated ramucirumab , a fully human anti-VEGFR-2 antibody , in patients with persistent or recurrent epithelial ovarian , fallopian tube , or primary peritoneal carcinoma . Primary endpoints were progression-free survival at 6 months ( PFS-6 ) and confirmed objective response rate ( ORR ) . METHODS Women who received ≥ 1 platinum-based chemotherapeutic regimen and had a platinum-free interval of < 12 months with measurable disease were eligible . Patients received 8 mg/kg ramucirumab intravenously every 2 weeks . RESULTS Sixty patients were treated ; one patient remained on study as of September 2013 . The median age was 62 years ( range : 27 - 80 ) , and median number of prior regimens was 3 . Forty-five ( 75 % ) patients had platinum refractory/resistant disease . Thirty-nine patients ( 65.0 % ) had serous tumors .  PFS-6 was 25.0 % ( n=15/60 , 95 % CI : 14.7 - 37.9 % ) . Best overall response was : partial response 5.0 % ( n=3/60 ) , stable disease 56.7 % ( n=34/60 ) , and progressive disease 33.3 % ( n=20/60 ) . The most common treatment-emergent adverse events possibly related to study drug were headache ( 65.0 % ; 10.0 % Grade ≥ 3 ) , fatigue ( 56.7 % ; 3.3 % Grade ≥ 3 ) , diarrhea ( 28.3 % ; 1.7 % Grade ≥ 3 ) , hypertension ( 25.0 % ; 3.3 % Grade ≥ 3 ) , and nausea ( 20.0 % ; no Grade ≥ 3 ) . Two patients experienced intestinal perforations ( 3.3 % Grade ≥ 3 ) . Pharmacodynamic analyses revealed changes in several circulating VEGF proteins following initial ramucirumab infusion , including increased VEGF-A , PlGF and decreased sVEGFR-2 . CONCLUSIONS Although antitumor activity was observed , the predetermined efficacy endpoints were not met 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 : To assess the efficacy and safety of the anti-VEGF receptor-2 ( VEGFR-2 ) antibody ramucirumab as first-line therapy in patients with advanced hepatocellular carcinoma and explore potential circulating biomarkers . Experimental Design : Adults with advanced hepatocellular carcinoma and no prior systemic treatment received ramucirumab 8 mg/kg every two weeks until disease progression or limiting toxicity . The primary endpoint was progression-free survival ( PFS ) ; secondary endpoints included objective response rate ( ORR ) and overall survival ( OS ) . Circulating biomarkers were evaluated before and after ramucirumab treatment in a subset of patients . Results : Forty-two patients received ramucirumab .  Median PFS was 4.0 months [ 95 % confidence interval ( CI ) , 2.6–5.7 ] , ORR was 9.5 % ( 95 % CI , 2.7–22.6 ; 4/42 patients had a partial response ) , and median OS was 12.0 months ( 95 % CI , 6.1–19.7 ) . For patients with Barcelona Clinic Liver Cancer ( BCLC ) stage C disease , median OS was 4.4 months ( 95 % CI , 0.5–9.0 ) for patients with Child-Pugh B cirrhosis versus 18.0 months ( 95 % CI , 6.1–23.5 ) for patients with Child-Pugh A cirrhosis . Treatment-related grade ≥3 toxicities included hypertension ( 14 % ) , gastrointestinal hemorrhage and infusion-related reactions ( 7 % each ) , and fatigue ( 5 % ) . There was one treatment-related death ( gastrointestinal hemorrhage ) . After treatment with ramucirumab , there was an increase in serum VEGF and placental growth factor ( PlGF ) and a transient decrease in soluble VEGFR-2 .  Conclusion : Ramucirumab monotherapy may confer anticancer activity in advanced hepatocellular carcinoma with an acceptable safety profile . Exploratory biomarker studies showed changes in circulating VEGF , PlGF , and sVEGFR-2 that are consistent with those seen with other anti-VEGF agents . Clin Cancer Res ; 19(23 ) ; 6614–23 . © 2013 AACR BACKGROUND Vascular endothelial growth factor ( VEGF ) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer . We aim ed to assess whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , prolonged survival in patients with advanced gastric cancer . METHODS We did an international , r and omised , double-blind , placebo-controlled , phase 3 trial between Oct 6 , 2009 , and Jan 26 , 2012 , at 119 centres in 29 countries in North America , Central and South America , Europe , Asia , Australia , and Africa . Patients aged 24 - 87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line platinum-containing or fluoropyrimidine-containing chemotherapy  were r and omly assigned ( 2:1 ) , via a central interactive voice-response system , to receive best supportive care plus either ramucirumab 8 mg/kg or placebo , intravenously once every 2 weeks . The study sponsor , participants , and investigators were masked to treatment assignment . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00917384 . FINDINGS 355 patients were assigned to receive ramucirumab ( n=238 ) or placebo ( n=117 ) . Median overall survival was 5·2 months ( IQR 2·3 - 9·9 ) in patients in the ramucirumab group and 3·8 months ( 1·7 - 7·1 ) in those in the placebo group ( hazard ratio [ 
    Output:
    
Hemorrhagic events associated with ramucirumab are modest and manageable while patients could continue to receive ramucizumab treatment to achieve their maximum clinical benefits