***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 BACKGROUND Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer . As part of the phase 1b KEYNOTE-012 study , we aim ed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction . METHODS This study was a multicentre , open-label , phase 1b trial done at 13 cancer research centres in the USA , Israel , Japan , South Korea , and Taiwan . We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction . Patients received intravenous pembrolizumab at 10 mg/kg once every 2 weeks for 24 months or until progression or  unacceptable toxic effects occurred . Response was assessed every 8 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 . The primary objectives were safety in patients who received at least one dose of pembrolizumab and the proportion of patients achieving overall responses in patients who received at least one pembrolizumab dose and who either had a post-baseline scan or who discontinued therapy because of clinical disease progression or a treatment-related adverse event before the first post-baseline scan . The study is registered with Clinical Trials.gov , number NCT01848834 , and is ongoing but no longer enrolling patients . FINDINGS From Oct 23 , 2013 , to May 5 , 2014 , 39 patients were enrolled . 36 were evaluable for response by central assessment . Eight ( 22 % , 95 % CI 10 - 39 ) patients were judged to have had an overall response at central review ; all responses were partial . All 39 patients were included in the safety analyses . Five ( 13 % ) patients had a total of six grade 3 or 4 treatment-related adverse events , consisting of two cases of grade 3 fatigue , one case each of grade 3 pemphigoid , grade 3 hypothyroidism , and grade 3 peripheral sensory neuropathy , and one case of grade 4 pneumonitis . No treatment-related deaths occurred . INTERPRETATION In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer , pembrolizumab had a manageable toxicity profile and promising antitumour activity , warranting further study in phase 2 and 3 trials . FUNDING Merck & 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 docetaxel can be recommended as an appropriate second-line treatment for patients with oesophagogastric adenocarcinoma that is refractory to treatment with platinum and fluoropyrimidine . FUNDING Cancer Research UK BACKGROUND The value of second-line therapy for metastatic gastric cancer is unclear . So far there are no r and omised phase III data comparing second-line chemotherapy to best supportive care ( BSC ) . In this prospect i ve , multicenter , open label , r and omised phase III study we compared irinotecan to BSC to evaluate the impact on survival of second-line chemotherapy . METHODS Eligible patients ( pts ) had metastatic or locally advanced gastro-oesophageal junction or gastric adenocarcinoma , objective tumour progression during or within 6months after first-line chemotherapy and ECOG performance status 0 - 2 . Stratification for time of progression after first-line therapy , ECOG PS and pretreatment secured even distribution of important prognostic factors . TREATMENT Arm A : Irinotecan 250mg/m(2)q3w ( first cycle ) to be increased to 350mg/m(2 ) , depending on toxicity . Arm B : BSC . FINDING 
    Output:
    
PD-1/PD-L1 inhibitors appear to improve the antitumor activity in advanced gastric or gastroesophageal junction cancer patients .
However , single-agent PD-1/PD-L1 inhibitor did not result in a relative improvement in OS and PFS compared with chemotherapy in the treatment of patients with advanced gastric or gastroesophageal junction cancer .