***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 : 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 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 Clinical data showed promising antitumour activity with feasible tolerability for matuzumab plus epirubicin , cisplatin and capecitabine ( ECX ) chemotherapy in untreated advanced oesophago-gastric ( OG ) cancer . The aim was to evaluate the efficacy of matuzumab plus ECX versus ECX alone . PATIENTS AND METHODS In this multicentre , r and omised open-label phase II study , 72 patients with metastatic OG cancer were r and omly assigned to either 800 mg matuzumab weekly plus epirubicin 50 mg/m² , cisplatin 60 mg/m² on day 1 and capecitabine 1250 mg/m² daily in a 21-day cycle ( ECX ) or the same ECX regimen alone . The primary end point was objective response . Secondary end points included progression-free survival ( PFS ) , overall survival ( OS ) , quality of life , safety and tolerability . RESULTS Following r and om assignment , 35 patients ( median age 59 years ) received ECX/matuzumab and 36 patients ( median age 64 years ) ECX . The addition of matuzumab to ECX did not improve objective response : 31 % for ECX/matuzumab [ 95 % confidence interval ( CI ) 17 - 49 ] compared with 58 % for the ECX arm ( 95 % CI 41 - 74 ) P = 0.994 ( one sided ) . There was no significant difference in median PFS : 4.8 months ( 95 % CI 2.9 - 8.1 ) for ECX/matuzumab versus 7.1 months ( 95 % CI 4.4 - 8.5 ) for ECX , or in median OS : 9.4 months ( 95 % CI 7.5 - 16.2 ) , compared with 12.2 months ( 95 % CI 9.8 - 13.8 months ) . Grade 3/4 treatment-related toxicity was observed in 27 and 25 patients in the ECX/matuzumab and ECX groups , respectively . CONCLUSION Matuzumab 800 mg weekly combined with ECX chemotherapy does not increase response or survival for patients with advanced OG cancer .  Therefore , ECX/matuzumab should not be examined further in phase III trials BACKGROUND Dysregulation of the hepatocyte growth factor (HGF)/MET pathway promotes tumour growth and metastasis . Rilotumumab is a fully human , monoclonal antibody that neutralises HGF . We aim ed to assess the safety , efficacy , biomarkers , and pharmacokinetics of rilotumumab combined with epirubicin , cisplatin , and capecitabine ( ECX ) in patients with advanced gastric or oesophagogastric junction cancer . METHODS We recruited patients ( ≥18 years old ) with unresectable locally advanced or metastatic gastric or oesophagogastric junction adenocarcinoma , an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 , who had not received previous systemic therapy , from 43 sites worldwide . Phase 1b was an open-label , dose de-escalation study to identify a safe dose of rilotumumab ( initial dose 15 mg/kg intravenously on day 1 ) plus ECX ( epirubicin 50 mg/m(2 ) intravenously on day 1 , cisplatin 60 mg/m(2 ) intravenously on day 1 , capecitabine 625 mg/m(2 ) twice a day orally on days 1 - 21 , respectively ) , administered every 3 weeks . The phase 1b primary endpoint was the incidence of dose-limiting toxicities in all phase 1b patients who received at least one dose of rilotumumab and completed the dose-limiting toxicity assessment window ( first cycle of therapy ) . Phase 2 was a double-blind study that r and omly assigned patients ( 1:1:1 ) using an interactive voice response system to receive rilotumumab 15 mg/kg , rilotumumab 7·5 mg/kg , or placebo , plus ECX ( doses as above ) , stratified by ECOG performance status and disease extent . The phase 2 primary endpoint was progression-free survival ( PFS ) , analysed by intention to treat . The study is registered with Clinical Trials.gov , number NCT00719550 . FINDINGS Seven of the nine patients enrolled in the phase 1b study received at least one dose of rilotumumab 15 mg/kg , only two of whom had three dose-limiting toxicities : palmar-plantar erythrodysesthesia , cerebral ischaemia , and deep-vein thrombosis . In phase 2 , 121 patients were r and omly assigned ( 40 to rilotumumab 15 mg/kg ; 42 to rilotumumab 7·5 mg/kg ; 39 to  placebo ) . Median PFS was 5·1 months ( 95 % CI 2·9 - 7·0 ) in the rilotumumab 15 mg/kg group , 6·8 months ( 4·5 - 7·5 ) in the rilotumumab 7·5 mg/kg group , 5·7 months ( 4·5 - 7·0 ) in both rilotumumab groups combined , and 4·2 months ( 2·9 - 4·9 ) in the placebo group . The hazard ratio for PFS events compared with placebo was 0·69 ( 80 % CI 0·49 - 0·97 ; p=0·164 ) for rilotumumab 15 mg/kg , 0·53 ( 80 % CI 0·38 - 0·73 ; p=0·009 ) for rilotumumab 7·5 mg/kg , and 0·60 ( 80 % CI 0·45 - 0·79 ; p=0·016 ) for combined rilotumumab . Any grade adverse events more common in the combined rilotumumab group than in the placebo group included haematological adverse events ( neutropenia in 44 [ 54 % ] of 81 patients vs 13 [ 33 % ] of 39 patients ; anaemia in 32 [ 40 % ] vs 11 [ 28 % ] ; and thrombocytopenia in nine [ 11 % ] vs none ) , peripheral oedema ( 22 [ 27 % ] vs three [ 8 % ] ) , and venous thromboembolism ( 16 [ 20 % ] vs five [ 13 % ] ) . Grade 3 - 4 adverse events more common with rilotumumab included neutropenia ( 36 [ 44 % ] vs 11 [ 28 % ] ) and venous thromboembolism ( 16 [ 20 % ] vs four [ 10 % ] ) . Serious adverse events were balanced between groups except for anaemia , which occurred more frequently in the combined rilotumumab group ( ten [ 12 % ] vs none ) . INTERPRETATION Rilotumumab plus ECX had no unexpected safety signals and showed greater activity than placebo plus ECX . A phase 3 study of the combination in MET-positive gastric and oesophagogastric junction cancer is in progress . FUNDING Amgen 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 [ 
    Output:
    
There is uncertainty about the effect of adding targeted therapy to chemotherapy on survival outcomes in people with advanced gastric cancer , with very little information on its impact on quality of life .
There is more certain evidence of increased risk of adverse events and serious adverse events .