***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 PURPOSE The first planned interim analysis ( median follow-up , 3 years ) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival , the primary end point . The results were therefore opened at the recommendation of an independent data and safety monitoring committee . We report 5-year follow-up data on patients enrolled onto the ACTS-GC study . PATIENTS AND METHODS Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were r and omly assigned to receive S-1 after surgery or surgery only . S-1 ( 80 to 120 mg per day ) was given for 4 weeks , followed by 2 weeks of rest . This 6-week cycle was repeated for 1 year . The primary end point was overall survival , and the secondary end points were relapse-free survival and safety . RESULTS The overall survival rate at 5 years was 71.7 % in the S-1 group and 61.1 % in the surgery-only group ( hazard ratio [ HR ] , 0.669 ; 95 % CI , 0.540 to 0.828 ) . The relapse-free survival rate at 5 years was 65.4 % in the S-1 group and 53.1 % in the surgery-only group ( HR , 0.653 ; 95 % CI , 0.537 to 0.793 ) . Subgroup analyses according to principal demographic factors such as sex , age , disease stage , and histologic type showed no interaction between treatment and any characteristic . CONCLUSION On the basis of 5-year follow-up data , postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy PURPOSE The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer . This international , double-blind , phase III study compared everolimus efficacy and safety with that of best supportive care ( BSC ) in previously treated advanced gastric cancer . PATIENTS AND METHODS Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were r and omly assigned to everolimus 10 mg/d ( assignment schedule : 2:1 ) or matching placebo , both given with BSC . R and omization was stratified by previous chemotherapy lines ( one v two ) and region ( Asia v rest of the world [ ROW ] ) . Treatment continued until disease progression or intolerable toxicity . Primary end point was overall survival ( OS ) . Secondary end points included progression-free survival ( PFS ) , overall response rate , and safety . RESULTS Six hundred fifty-six patients ( median age , 62.0 years ; 73.6 % male ) were enrolled .  Median OS was 5.4 months with everolimus and 4.3 months with placebo ( hazard ratio , 0.90 ; 95 % CI , 0.75 to 1.08 ; P = .124 ) . Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms , respectively ( hazard ratio , 0.66 ; 95 % CI , 0.56 to 0.78 ) . Common grade 3/4 adverse events included anemia , decreased appetite , and fatigue . The safety profile was similar in patients enrolled in Asia versus ROW . CONCLUSION Compared with BSC , everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy . The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea  ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche BACKGROUND Second-line chemotherapy for patients with oesophagogastric adenocarcinoma refractory to platinum and fluoropyrimidines has not shown benefits in health-related quality of life ( HRQoL ) . We assessed whether the addition of docetaxel to active symptom control alone can improve survival and HRQoL for patients . METHODS For this open-labelled , multicentre trial , we recruited patients aged 18 years or older from 30 UK centres . Patients were eligible if they had an advanced , histologically confirmed adenocarcinoma of the oesophagus , oesophagogastric junction , or stomach that had progressed on or within 6 months of treatment with a platinum-fluoropyrimidine combination . Patients could have an Eastern Cooperative Oncology Group performance status of 0 - 2 . We r and omly assigned patients using a central , computerised minimisation procedure to receive docetaxel plus active symptom control , or active symptom control alone ( 1:1 ; stratified by disease status , disease site , duration of response to previous chemotherapy , and performance status ) . Docetaxel was given at a dose of 75 mg/m(2 ) by intravenous infusion every 3 weeks for up to six cycles . The primary endpoint was overall survival , analysed by intention to treat . This is the report of the planned final analysis . This study is an International St and ardised R and omised Controlled Trial , number IS RCT N13366390 . FINDINGS Between April 21 , 2008 , and April 26 , 2012 , we recruited 168 patients , allocating 84 to each treatment group . After a median follow-up of 12 months [ IQR 10 - 21 ] ) and 161 ( 96 % ) deaths ( 80 in the docetaxel group , 81 in the active symptom control group ) , median overall survival in the docetaxel group was 5.2 months ( 95 % CI 4.1 - 5.9 ) versus 3.6 months ( 3.3 - 4.4 ) in the active symptom control group ( hazard ratio 0.67 , 95 % CI 0.49 - 0.92 ; p=0.01 ) . Docetaxel was associated with higher incidence of grade 3 - 4 neutropenia ( 12 [ 15 % ] patients vs no patients ) , infection ( 15 [ 19 % ] patients vs two [ 3 % ] patients ) , and febrile neutropenia ( six [ 7 % ] patients vs no patients ) . Patients receiving docetaxel reported less pain ( p=0.0008 ) and less nausea and vomiting ( p=0.02 ) and constipation ( p=0.02 ) . Global HRQoL was similar between the groups ( p=0.53 ) . Disease specific HRQoL measures also showed benefits for docetaxel in reducing dysphagia ( p=0.02 ) and abdominal pain ( p=0.01 ) . INTERPRETATION Our findings suggest that docet 
    Output:
    
With available evidence , the use of TAs in GC patients was associated with an increased risk of severe AEs , but not for FAE .