***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 The Trastuzumab for Gastric Cancer ( ToGA ) study is the first international trial to include Japanese patients with human epidermal growth factor 2 ( HER2 ) positive advanced/metastatic gastric or gastroesophageal junction cancer . ToGA showed that trastuzumab plus chemotherapy ( capecitabine/cisplatin or 5-fluorouracil/cisplatin ) improved overall survival in the overall population ( hazard ratio 0.74 ) . Regional differences in outcome in favor of Japanese population s were observed in other studies ; therefore , subgroup analyses of ToGA may contribute to the evaluation of the potential benefits of this regimen in Japanese patients . Methods We performed subgroup analyses on 101 Japanese patients enrolled into ToGA ( trastuzumab plus chemotherapy , n = 51 ; chemotherapy , n = 50 ) . Results Median overall survival in the Japanese subgroup was 15.9 months ( 95 % confidence interval 12–25 ) for trastuzumab plus chemotherapy and 17.7 months ( 95 % confidence interval 12–24 ) for chemotherapy ( hazard ratio 1.00 ; 95 % confidence interval 0.59–1.69 ) . After adjusting for prespecified covariates , the estimated hazard ratio for overall survival was 0.68 ( 95 % confidence interval 0.36–1.27 ) . Further post hoc and exploratory examinations supported the robustness of the adjusted hazard ratios . Conclusions After adjusting for imbalanced patient background s between arms , overall survival of Japanese patients with human epidermal growth factor 2 positive advanced/metastatic gastric or gastroesophageal junction cancer who received trastuzumab plus chemotherapy was improved compared with patients who received chemotherapy alone Objective : To better underst and the clinical implication s of insulin-like growth factor type 1 receptor ( IGF-1R ) , epidermal growth factor receptor ( EGFR ) and HER2 expressions in gastric cancer ( GC ) . Methods : The study group comprised 86 patients who received first-line chemotherapy for advanced GC at the National Cancer Center Hospital . Using laser-captured microdissection and a real-time RT-PCR assay , we quantitatively evaluated mRNA levels of IGF-1R , EGFR and HER2 in paraffin-embedded cancer specimens of surgically removed primary tumors . Results : In univariate analysis of the study group as a whole , patients with low expression of both IGF-1R and EGFR ( n = 13 ) had a significantly longer overall survival than the other patients ( n = 51 ; median , 24.6 vs. 12.8 months ; log-rank p = 0.013 ) . Multivariate survival analysis demonstrated that high EGFR expression [ hazard ratio , HR : 2.94 ( 95 % confidence interval , CI : 1.40–6.17 ) , p = 0.004 ] and poor performance status [ HR : 1.96 ( 95 % CI : 1.12–3.42 ) , p = 0.018 ] were significant predictors of poor survival . In patients given first-line S-1 monotherapy ( n = 29 ) , low IGF-1R ( p = 0.002 ) and low EGFR ( p = 0.035 ) gene expression correlated with a better response , without a significant prolongation of survival . Conclusion : Our data warrant further investigations on the strategy of co-targeting IGF-1R and EGFR in GC 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 Purpose : EGF receptor ( EGFR ) and HER2 positivity are considered to be negative prognostic factors in gastric cancer . Biomarker analysis was conducted to evaluate the impact of EGFR and HER2 expression on the outcome of patients enrolled in the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer ( ACTS-GC ) , a r and omized controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients with stage II/III gastric cancer . Experimental Design :  Formalin-fixed , paraffin-embedded surgical specimens were retrospectively examined in 829 patients ( 78.3 % ) . The effects of EGFR and HER2 positivity on survival were analyzed on the basis of the 5-year survival data from the study . EGFR positivity was defined as an immunohistochemistry ( IHC ) score of 3 + , and HER2 positivity as an IHC score of 3 + or an IHC score of 2 + with a positive dual-color in situ hybridization status . Results : EGFR and HER2 were positive in 75 ( 9.0 % ) and 113 ( 13.6 % ) patients , respectively . The overall and relapse-free survival rates were significantly lower in EGFR-positive patients than in EGFR-negative patients , whereas they were similar in HER2-positive and HER2-negative patients . Multivariate analysis showed that EGFR positivity correlated with poor outcomes [ HR = 1.504 ; 95 % confidence interval ( CI ) = 1.020–2.149 ; P = 0.040 ] . Treatment with S-1  improved survival compared with surgery alone , irrespective of EGFR and HER2 status . Conclusions : EGFR positivity , but not HER2 positivity , was associated with poor patient outcomes after curative resection of stage II/III gastric cancer . There was no interaction between S-1 and EGFR or HER2 status with respect to survival outcome . Clin Cancer Res ; 18(21 ) ; 5992–6000 . © 2012 AACR The optimal adjuvant treatment for gastric cancer remains controversial . We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen , in patients with high-risk gastric cancer , with that of the same chemotherapy plus radiation therapy ( RT ) . In addition , we evaluated the prognostic and /or predictive value of a panel of molecular markers . Patients with histologically proven , radically resected gastric cancer , stage ≥T3 and /or N+ were r and omized to 6 cycles of docetaxel with cisplatin , both at 75 mg/m2 every 3 weeks ( arm A ) or the same treatment with RT ( arm B ; 45 Gy ) . Due to excessive nausea and vomiting , cisplatin was substituted by carboplatin at AUC ( area under the curve ) of 5 after the first 45 patients ( 22 group A , 23 group B ) . The prognostic value of EGFR , ERCC1 , HER2 , MET/HGFR , MAP-Tau , and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays ( TMAs ) . A total of 147 patients were r and omized . After a median follow-up of 53.7 months , no differences in overall ( OS ) and disease-free survival ( DFS ) were found between the two arms . The most common grade 3/4 toxicities for arms A and B ( excluding alopecia ) were non-febrile neutropenia ( 11 and 17 % , respectively ) , febrile neutropenia ( 9 and 7 % ) and diarrhea ( 7 and 4 % , respectively ) . Patients with ERCC1 positive tumors had significantly longer median DFS ( 33.1 vs. 11.8 months , Wald P = 0.016 ) and OS ( 63.2 vs. 18.8 months , Wald P = 0.046 ) . Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk , radically resected gastric cancer . However , the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded BACKGROUND Cetuximab plus irinotecan/folinic acid/5-fluorouracil ( 5-FU ) ( IF ) was evaluated as first-line treatment of patients with advanced gastric cancer and gastroesophageal junction tumors . Preplanned analyses of the influence of tumor biomarkers on treatment outcome were carried out . PATIENTS AND METHODS Patients received weekly cetuximab ( 400 mg/m(2 ) on day 1 , subsequently 250 mg/m(2 ) ) plus irinotecan ( 80 mg/m(2 ) ) and a 24-hour continuous infusion of folinic acid ( 200 mg/m(2 ) ) and 5-FU ( 1500 mg/m(2 ) ) on days 1 , 8 , 15 , 22 , 29 and 36 of a 50-day cycle , until progressive disease ( PD ) . RESULTS The most common grade 3/4 toxic effects in 49 patients were diarrhea ( 15 % ) and skin toxic effects ( 14 % ) . In 48 assessable patients , the overall response rate was 46 % and disease control rate was 79 % . Median progression-free survival ( PFS ) and overall survival ( OS ) was 9.0 months [ 95 % confidence interval ( CI ) 7.1 - 15.6 ] and 16.5 months ( 95 % CI 11.7 - 30.1 ) , respectively . Tumor response was more common than nonresponse in epidermal growth factor receptor-expressing tumors ( P = 0.041 ) . Tumor PTEN expression was associated with longer PFS ( P = 0.035 ) and OS ( P = 0.0127 ) than no PTEN expression . CONCLUSION Cetuximab plus IF was well tolerated and efficacy data were encouraging . This treatment combination and the role of selected biomarkers are under investigation in the ongoing phase III EXP AND trial 
    Output:
    
This meta- analysis result suggested that EGFR or HER2 should have significant predictive ability for estimating overall survival in GC patients and may be useful for defining prognosis of GC patients