***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 VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis . Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist . We aim ed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib . METHODS In this r and omised , placebo-controlled , double-blind , multicentre , phase 3 trial ( REACH ) , patients were enrolled from 154 centres in 27 countries . Eligible patients were aged 18 years or older , had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy , had Child-Pugh A liver disease , an Eastern Cooperative Oncology Group performance status of 0 or 1 , had previously received sorafenib ( stopped because of progression or intolerance ) , and had adequate haematological and biochemical parameters . Patients were r and omly assigned ( 1:1 ) to receive intravenous ramucirumab ( 8 mg/kg ) or placebo every 2 weeks , plus best supportive care , until disease progression , unacceptable toxicity , or death . R and omisation was stratified by geographic region and cause of liver disease with a stratified permuted block method . Patients , medical staff , investigators , and the funder were masked to treatment assignment . The primary endpoint was overall survival in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT01140347 . FINDINGS Between Nov 4 , 2010 , and April 18 , 2013 , 565 patients were enrolled , of whom 283 were assigned to ramucirumab and 282 were assigned to placebo . Median overall survival for the ramucirumab group was 9·2 months ( 95 % CI 8·0 - 10·6 ) versus 7·6 months ( 6·0 - 9·3 ) for the placebo group ( HR 0·87 [ 95 % CI 0·72 - 1·05 ] ; p=0·14 ) . Grade 3 or greater adverse events occurring in 5 % or more of patients in either treatment group were ascites ( 13 [ 5 % ] of 277 patients treated with ramucirumab vs 11 [ 4 % ] of 276 patients treated with placebo ) , hypertension ( 34 [ 12 % ] vs ten [ 4 % ] ) , asthenia ( 14 [ 5 % ] vs five [ 2 % ] ) , malignant neoplasm progression ( 18 [ 6 % ] vs 11 [ 4 % ] ) , increased aspartate aminotransferase concentration ( 15 [ 5 % ] vs 23 [ 8 % ] ) , thrombocytopenia ( 13 [ 5 % ] vs one [ < 1 % ] ) , hyperbilirubinaemia ( three [ 1 % ] vs 13 [ 5 % ] ) , and increased blood bilirubin ( five [ 2 % ] vs 14 [ 5 % ] ) . The most frequently reported ( ≥1 % ) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression . INTERPRETATION Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma . No new safety signals were noted in eligible patients and the safety profile is manageable . FUNDING Eli Lilly and PURPOSE This phase II study of sorafenib , an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases , assessed efficacy , toxicity , pharmacokinetics , and biomarkers in advanced hepatocellular carcinoma ( HCC ) patients . METHODS Patients with inoperable HCC , no prior systemic treatment , and Child-Pugh ( CP ) A or B , received continuous , oral sorafenib 400 mg bid in 4-week cycles . Tumor response was assessed every two cycles using modified WHO criteria . Sorafenib pharmacokinetics were measured in plasma sample s. Biomarker analysis included phosphorylated extracellular signal regulated kinase ( pERK ) in pretreatment biopsies ( immunohistochemistry ) and blood-cell RNA expression patterns in selected patients . RESULTS Of 137 patients treated ( male , 71 % ; median age , 69 years ) , 72 % had CP A , and 28 % had CP B. On the basis of independent assessment , three ( 2.2 % ) patients achieved a partial response , eight ( 5.8 % ) had a minor response , and 46 ( 33.6 % ) had stable disease for at least 16 weeks . Investigator-assessed median time to progression ( TTP ) was 4.2 months , and median overall survival was 9.2 months . Grade 3/4 drug-related toxicities included fatigue ( 9.5 % ) , diarrhea ( 8.0 % ) , and h and -foot skin reaction ( 5.1 % ) . There were no significant pharmacokinetic differences between CP A and B patients . Pretreatment tumor pERK levels correlated with TTP . A panel of 18 expressed genes was identified that distinguished " nonprogressors " from " progressors " with an estimated 100 % accuracy . CONCLUSION Although single-agent sorafenib has modest efficacy in HCC , the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents 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 BACKGROUND The efficacy and safety of axitinib , a potent and selective vascular endothelial growth factor receptors 1 - 3 inhibitor , combined with best supportive care ( BSC ) was evaluated in a global , r and omized , placebo-controlled phase II trial in patients with locally advanced or metastatic hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS Patients with HCC and Child-Pugh Class A who progressed on or were intolerant to one prior antiangiogenic therapy were stratified by tumour invasion ( presence/absence of extrahepatic spread and /or vascular invasion ) and region ( Asian/non-Asian ) and r and omized ( 2:1 ) to axitinib/BSC ( starting dose 5 mg twice-daily ) or placebo/BSC . The primary end point was overall survival ( OS ) . RESULTS The estimated hazard ratio for OS was 0.907 [ 95 % confidence interval ( CI ) 0.646 - 1.274 ; one-sided stratified P = 0.287 ] for axitinib/BSC ( n = 134 ) versus placebo/BSC ( n = 68 ) , with the median ( 95 % CI ) of 12.7 ( 10.2 - 14.9 ) versus 9.7 ( 5.9 - 11.8 ) months , respectively . Results of prespecified subgroup analyses in Asian versus non-Asian patients or presence versus absence of tumour invasion were consistent with the overall population . Improvements favouring axitinib/BSC ( P < 0.01 ) were observed in secondary efficacy end point analyses [ progression-free survival ( PFS ) , time to tumour progression ( TTP ) , and clinical benefit rate ( CBR ) ] , and were retained among Asian patients in the prespecified subgroup analyses . Overall response rate did not differ significantly between treatments and patient-reported outcomes favoured placebo/BSC . Most common all-causality adverse events with axitinib/BSC  were diarrhoea ( 54 % ) , hypertension ( 54 % ) , and decreased appetite ( 47 % ) . Baseline serum analyses identified potential new prognostic ( interleukin-6 , E-selectin , interleukin-8 , angiopoietin-2 , migration inhibitory factor , and c-MET ) or predictive ( E-selectin and stromal-derived factor-1 ) factors for survival . CONCLUSIONS Axitinib/BSC did not improve OS over placebo/BSC in the overall population or in stratification subgroups . However , axitinib/BSC result ed in significantly longer PFS and TTP and higher CBR , with acceptable toxicity in patients with advanced HCC . TRIAL REGISTRATION Clinical Trials.gov , NCT01210495 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 ram 
    Output:
    
Conclusions The findings of this study show that elderly HCC patients who relapsed after a first-line sorafenib treatment obtains a survival benefits from anti-VEGF agents rechallenge .