***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 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 Background YN968D1 ( Apatinib ) selectively inhibits phosphorylation of VEGFR-2 and tumor angiogenesis in mice model . The study was conducted to determine the maximum tolerated dose ( MTD ) , safety profile , pharmacokinetic variables , and antitumor activity in advanced solid malignancies . Methods This dose-escalation study was conducted according to the Chinese State Food and Drug Administration ( S FDA ) recommendations in patients with advanced solid tumors to determine the MTD for orally administered apatinib . Doses of continuously administered apatinib were escalated from 250 mg . Treatment continued after dose-escalation phase until withdrawal of consent , intolerable toxicities , disease progression or death . Results Forty-six patients were enrolled .  Hypertension and h and -foot syndrome were the two dose-limiting toxicities noted at dose level of 1000 mg . MTD was determined to be 850 mg once daily . Pharmacokinetic analysis showed early absorption with a half-life of 9 hours . The mean half-life was constant over all dose groups . Steady-state conditions analysis suggested no accumulation during 56 days of once-daily administration . The most frequently observed drug-related adverse events were hypertension ( 69.5 % , 29 grade 1 - 2 and 3 grade 3 - 4 ) , proteinuria ( 47.8 % , 16 grade 1 - 2 and 6 grade 3 - 4 ) , and h and -foot syndrome ( 45.6 % , 15 grade 1 - 2 and 6 grade 3 - 4 ) . Among the thirty-seven evaluable patients , PR was noted in seven patients ( 18.9 % ) , SD 24 ( 64.9 % ) , with a disease control rate of 83.8 % at 8 weeks . Conclusions The recommended dose of 750 mg once daily was well tolerated . Encouraging antitumor activity across a broad range of malignancies warrants further evaluation in selected population s . Trial registration Clinical Trials.gov unique identifier : 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 Angiogenesis is an important process in cell development , especially in cancer . Vascular endothelial growth factor ( VEGF ) signaling is an important regulator of angiogenesis . Several therapies that act against VEGF signal transduction have been developed , including YN968D1 , which is a potent inhibitor of the VEGF signaling pathway . This study investigated the antitumor activity of YN968D1 ( apatinib mesylate ) in vitro and in vivo . YN968D1 potently suppressed the kinase activities of VEGFR‐2 , c‐kit and c‐src , and inhibited cellular phosphorylation of VEGFR‐2 , c‐kit and PDGFRβ . YN968D1 effectively inhibited proliferation , migration and tube formation of human umbilical vein endothelial cells induced by FBS , and blocked the budding of rat aortic ring . In vivo , YN968D1 alone and in combination with chemotherapeutic agents effectively inhibited the growth of several established human tumor xenograft models with little toxicity . A phase I study of YN968D1 has shown encouraging antitumor activity and a manageable toxicity profile . These findings suggest that YN968D1 has promise as an antitumor drug and might have clinical benefits . ( Cancer Sci 2011 ; 102 : 1374–1380 BACKGROUND A regimen of epirubicin , cisplatin , and infused fluorouracil ( ECF ) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma . We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer . METHODS We r and omly assigned patients with resectable adenocarcinoma of the stomach , esophagogastric junction , or lower esophagus to either perioperative chemotherapy and surgery ( 250 patients ) or surgery alone ( 253 patients ) . Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin ( 50 mg per square meter of body-surface area ) and cisplatin ( 60 mg per square meter ) on day 1 , and a continuous intravenous infusion of fluorouracil ( 200 mg per square meter per day ) for 21 days . The primary end point was overall survival . RESULTS  ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer .  Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group ( 46 percent and 45 percent , respectively ) , as were the numbers of deaths within 30 days after surgery . The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group . With a median follow-up of four years , 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died . As compared with the surgery group , the perioperative-chemotherapy group had a higher likelihood of overall survival ( hazard ratio for death , 0.75 ; 95 percent confidence interval , 0.60 to 0.93 ; P=0.009 ; five-year survival rate , 36 percent vs. 23 percent ) and of progression-free survival ( hazard ratio for progression , 0.66 ; 95 percent confidence interval , 0.53 to 0.81 ; P<0.001 ) . CONCLUSIONS In patients with operable gastric or lower esophageal adenocarcinomas , a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival . ( Current Controlled Trials number , IS RCT N93793971 [ controlled-trials.com ] . ) 
    Output:
    
Compare ramucirumab and bevacizumab in combination with traditional chemotherapy ; ramucirumab has shown to improve progression-free survival and overall survival .
Apatinib tyrosine kinase inhibitor combined with traditional chemotherapy has shown to improve overall response rate and progression-free survival with marginal improvements in overall survival .
Chemotherapy , in combination with anti-VEGF drugs , in the management of advanced gastric cancer significantly improves the outcome of overall response rate , progression-free survival and overall survival when compared to chemotherapy alone .