***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 : This study aim ed to determine whether combination S-1 plus cisplatin ( CDDP ) therapy , the most widely used therapy for Japanese patients with advanced gastric cancer , and the novel oral antiangiogenic agent TSU-68 could contribute to gastric cancer treatment . Methods : Ninety-three patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers were r and omised into two groups : TSU-68 plus S-1/CDDP ( group A ) and S-1/CDDP ( group B ) groups . Both patient groups received identical S-1 and CDDP dosages . TSU-68 was orally administered for 35 consecutive days . Group B patients received S-1 orally twice daily for three consecutive weeks , followed by intravenous CDDP on day 8 . The primary endpoint was progression-free survival ( PFS ) . Results : Median PFS periods were 208 and 213 days in groups A and B , respectively ( P=0.427 ) . Median survival periods for groups A and B were 497.0 and 463.5 days , respectively ( P=0.219 ) . No statistically significant differences were noted for PFS , survival or the adverse event ( AE ) incidence rate . All AEs were expected according to previous reports for TSU-68 , TS-1 , and CDDP . Conclusion : Combination therapy involving TSU-68 , S-1 , and CDDP was safe and well tolerated in patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers . However , factors related to therapeutic efficacy should be investigated further PURPOSE We evaluated the activity of regorafenib , an oral multikinase inhibitor , in advanced gastric adenocarcinoma . PATIENTS AND METHODS We conducted an international ( Australia and New Zeal and , South Korea , and Canada ) r and omized phase II trial in which patients were r and omly assigned at a two-to-one ratio and stratified by lines of prior chemotherapy for advanced disease ( one v two ) and region . Eligible patients received best supportive care plus regorafenib 160 mg or matching placebo orally on days 1 to 21 of each 28-day cycle until disease progression or prohibitive adverse events occurred . The primary end point was progression-free survival ( PFS ) . Final analysis included data to December 31 , 2014 . RESULTS A total of 152 patients were r and omly assigned from November 7 , 2012 , to February 25 , 2014 , yielding 147 evaluable patients ( regorafenib , n = 97 ; placebo , n = 50 ) . Baseline characteristics were balanced . Median PFS significantly differed between groups ( regorafenib , 2.6 months ; 95 % CI , 1.8 to 3.1 and placebo , 0.9 months ; 95 % CI , 0.9 to 0.9 ; hazard ratio [ HR ] , 0.40 ; 95 % CI , 0.28 to 0.59 ; P < .001 ) . The effect was greater in South Korea than in Australia , New Zeal and , and Canada combined ( HR , 0.12 v 0.61 ; interaction P < .001 ) but consistent across age , neutrophil-to-lymphocyte ratio , primary site , lines of chemotherapy , peritoneal metastasis presence , number of metastatic sites , and plasma vascular endothelial growth factor A. A survival trend in favor of regorafenib was seen ( median , 5.8 months ; 95 % CI , 4.4 to 6.8 v 4.5 months ; 95 % CI , 3.4 to 5.2 ; HR , 0.74 ; P = .147 ) . Twenty-nine patients assigned to placebo received open-label regorafenib after disease progression . Regorafenib toxicity was similar to that previously reported . CONCLUSION In this phase II trial , regorafenib was effective in prolonging PFS in refractory advanced gastric adenocarcinoma . Regional differences were found , but regorafenib was effective in both regional groups . A phase III trial is planned 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 As a multi-targeted anti-angiogenic receptor tyrosine kinase ( RTK ) inhibitor sunitinib ( SUN ) has been established for renal cancer and gastrointestinal stromal tumors . In advanced refractory esophagogastric cancer patients , monotherapy with SUN was associated with good tolerability but limited tumor response . Methods This double-blind , placebo-controlled , multicenter , phase II clinical trial was conducted to evaluate the efficacy , safety and tolerability of SUN as an adjunct to second and third-line FOLFIRI ( NCT01020630 ) . Patients were r and omized to receive 6-week cycles including FOLFIRI plus sodium folinate ( Na-FOLFIRI ) once every two weeks and SUN or placebo ( PL ) continuously for four weeks followed by a 2-week rest period . The primary study endpoint was progression-free survival ( PFS ) . Preplanned serum analyses of VEGF-A , VEGF-D , VEGFR2 and SDF-1α were performed retrospectively . Results Overall , 91 patients were r and omized , 45 in each group ( one patient withdrew ) . The main grade ≥3 AEs were neutropenia and leucopenia , observed in 56 % /20 % and 27 % /16 % for FOLFIRI + SUN/FOLFIRI + PL , respectively . Median PFS was similar , 3.5 vs. 3.3 months ( hazard ratio ( HR ) 1.11 , 95 % CI 0.70–1.74 , P = 0.66 ) for FOLFIRI + SUN vs. FOLFIRI + PL , respectively . For FOLFIRI + SUN , a trend towards longer median overall survival ( OS ) compared with placebo was observed ( 10.4 vs. 8.9 months , HR 0.82 , 95 % CI 0.50–1.34 , one-sided P = 0.21 ) . In subgroup serum analyses , significant changes in VEGF-A ( P = 0.017 ) , VEGFR2 ( P = 0.012 ) and VEGF-D ( P < 0.001 ) serum levels were observed . Conclusions Although sunitinib combined with FOLFIRI did not improve PFS and response in chemotherapy-resistant gastric cancer , a trend towards better OS was observed . Further biomarker-driven studies with other anti-angiogenic RTK inhibitors are warranted . Trial registration This study was registered prospect ively in the NCT Clinical Trials Registry ( Clinical Trials.gov ) under NCT01020630 on November 23 , 2009 after approval by the leading ethics committee of the Medical Association of Rhinel and -Palatinate , Main 
    Output:
    
Conclusions The addition of AAs to st and ard therapy in mOGC improves OS .
Improved efficacy was only observed in 2nd- or 3rd-line setting and not in 1st-line setting .
Consistent OS benefit was present across all geographical regions .
This benefit is at the expense of increased overall toxicity