***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 
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    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 Summary Background Cisplatin and fluoropyrimidine ( CF ) are st and ard first- line treatment in advanced gastric cancer , but no second-line treatment has yet been established . We present a phase II study in which we evaluated the efficacy and toxicity of the combination of Sorafenib ( S ) , and Oxaliplatin as second-line therapy . Methods Patients with progressive gastric adenocarcinoma after CF- first-line , ECOG 0–2 , and measurable disease were included . The primary objective was PFS . Treatment doses were Oxaliplatin 130 mg/m2/3 weeks and Sorafenib 800 mg/bid/d . Results We included 40 patients . CR was 2.5 % and SD was 47.2 % . Grade 3–4 toxic effects were neutropenia ( 9.8 % ) , thrombocytopenia ( 7.3 % ) , neurotoxicity ( 4.9 % ) and diarrhea ( 4.9 % ) . Median PFS was 3 months ( 95 % CI : 2.3–4.1 ) and median OS was 6.5 months ( 95 % CI : 5.2–9.6 ) . Time to progression ( TTP ) to first line therapy was a prognosis factor . Median OS was 9.7 months when time-to-progression during first-line chemotherapy was > 6 months and 5.6 m when it was < 6 months ( p = 0.04 ) . Conclusions Time-to-progression under a CF-based first-line therapy determines subgroups of GC patients with different prognosis . The combination of Oxaliplatin-Sorafenib in advanced GC patients previously treated with CF appears safe , but our results do not support the implementation of a phase III trial Summary Purpose . This phase II , open-label , multicenter study assessed the oral , multitargeted , tyrosine kinase inhibitor sunitinib in patients with advanced gastric or gastroesophageal junction adenocarcinoma who had received prior chemotherapy . Experimental design . Patients received sunitinib 50 mg/day on Schedule 4/2 ( 4 weeks on treatment , followed by 2 weeks off treatment ) . The primary endpoint was objective response rate ; secondary endpoints included clinical benefit rate , duration of response , progression-free survival ( PFS ) , overall survival ( OS ) , pharmacokinetics , pharmacodynamics , safety and tolerability , and quality of life . Results . Of 78 patients enrolled , most had gastric adenocarcinoma ( 93.6 % ) and metastatic disease ( 93.6 % ) . All were evaluable for safety and efficacy . Two patients ( 2.6 % ) had partial responses and 25 patients ( 32.1 % ) had a best response of stable disease for ≥6 weeks . Median PFS was 2.3 months ( 95 % confidence interval [ CI ] , 1.6–2.6 months ) and median OS was 6.8 months ( 95 % CI , 4.4–9.6 months ) . Grade ≥3 thrombocytopenia and neutropenia were reported in 34.6 % and 29.4 % of patients , respectively , and the most common non-hematologic adverse events were fatigue , anorexia , nausea , diarrhea , and stomatitis . Pharmacokinetics of sunitinib and its active metabolite were consistent with previous reports . There were no marked associations between baseline soluble protein levels , or changes from baseline , and measures of clinical outcome . Conclusions . The progression-delaying effect and manageable toxicity observed with sunitinib in this study suggest that although single-agent sunitinib has insufficient clinical value as second-line treatment for advanced gastric cancer , its role in combination with chemotherapy merits further study 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 Introduction Current treatment options for advanced esophagogastric cancer ( AEGC ) are still unsatisfactory . The aim of this prospect i ve phase Ib/II study was to evaluate the safety and efficacy of a novel regimen , AVDCX , consisting of weekly docetaxel and cisplatin together with capecitabine and bevacizumab , in AEGC . Methods Patients with AEGC received treatment with different dose levels of AVDCX ( cisplatin and docetaxel 25–35 mg/m2 , days 1,8 , capecitabine 1,600 mg/m2 days 1–14 , bevacizumab 7.5 mg/kg , day 1 , Q:21 days ) . The study 's primary objectives were to establish the recommended phase II doses of docetaxel and cisplatin in AVDCX ( phase Ib part ) and to determine the tumor response rate ( phase II part ) . Results The study was closed early , after the accrual of 22 patients , due to accumulating toxicity-related deaths . The median age was 59 years and 77 % of patients had gastric or gastroesophageal adenocarcinomas .  Grade ≥3 adverse events were documented in 18 patients ( 82 % ) , usually neutropenia ( 36 % ) , fatigue ( 54 % ) or diarrhea ( 23 % ) . There were three fatal toxicities ( 14 % ) : mesenteric thromboembolism , gastric perforation and pancytopenic sepsis . The recommended phase II doses of cisplatin and docetaxel were determined to be 25 mg/m2 and 30 mg/m2 , respectively . Twenty-one patients were evaluable for response : 12 ( 54 % ) had partial response ( PR ) , 4 ( 18 % ) had stable disease ( SD ) and none had complete response ( CR ) . Hence , the objective response rate ( CR+PR ) was 54 % and the disease control rate ( CR+PR+SD ) was 72 % . For the 17 patients treated at the MTD , the objective response rate was 41 % and the disease control rate was 88 % . The median overall survival ( OS ) for these patients was 13.9 months ( range , 1.5–52.2 months ) and the median progression-free survival was 7.6 months ( range , 1.3–26.6 months ) . The 2-year OS rate reached 23.7 % . Conclusions AVDCX was associated with a high rate of regimen related fatal adverse events and is not appropriate for further development in AEGC patients . Trial Registration Clinical Trials.gov NCT00845884 Summary Background To define maximum-tolerated dose ( MTD ) , dose-limiting toxicities ( DLTs ) , and preliminary efficacy of sorafenib plus capecitabine/cisplatin in advanced gastric cancer ( AGC ) patients . Methods Four dose-level combinations were tested in a st and ard 3 + 3 dose escalation design . Level 1 : sorafenib 400 mg/d , capecitabine 1,600 mg/m2/d , cisplatin 80 mg/m2 . Level 2 : sorafenib 800 mg/d , capecitabine 1,600 mg/m2/d , cisplatin 80 mg/m2 . Level 3 : sorafenib 800 mg/d , capecitabine 2,000 mg/m2/d , cisplatin 80 mg/m2 . Level 1A : sorafenib 800 mg/d , capecitabine 1,600 mg/m2/d , cisplatin 60 mg/m2 . Results There were 1 DLT at Level 2 , and 2 DLTs at Level 3 ( Level 3 was MTD ) . 
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In addition , patients treated with VEGF or VEGFR blockers had higher morbidity of hypertension and neutropenia , but lower risk of side effects of vomiting and anemia .
These findings suggest that addition of antiangiogenesis reagents , especially anti-VEGFR-mAb , to the first- or second-line chemotherapy could prolong patient 's OS and PFS time in the advanced or metastatic gastric cancer