title: Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data.
abstract: BACKGROUND
  Second-line chemotherapy treatment of patients with relapsed gastric and oesophageal cancers in comparison with supportive care (SC) alone has been supported by recent phase 3 clinical trials, but a meta-analysis of patient-level data is lacking.
  
  
  METHODS
  We searched Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Web of Science for phase 3 clinical trials that compared second-line chemotherapy with SC alone for gastric and oesophageal cancers. A meta-analysis of the comprehensive patient-level data from the three identified trials was performed.
  
  
  RESULTS
  A total of 410 patients with gastric (n=301), gastroesophageal junction (n=76), or oesophageal (n=33) adenocarcinoma were identified. In all, 154 patients received single-agent docetaxel and 84 patients received single-agent irinotecan, each with SC. SC alone was given to 172 patients. Chemotherapy significantly reduced the risk of death (hazard ratio (HR)=0.63, 95% confidence interval (CI)=0.51-0.77, P<0.0001). This effect was observed for treatment with docetaxel (HR=0.71, 95% CI=0.56-0.89, P=0.003) and irinotecan (HR=0.49, 95% CI=0.36-0.67, P<0.001). Overall survival (OS) benefit was greatest for patients who progressed 3-6 months following first-line chemotherapy (HR=0.39, 95% CI=0.26-0.59, P<0.0001). Performance status (PS) 0-1 compared with PS 2 (HR=0.66, 95% CI=0.46-0.94, P=0.02), locally advanced disease compared with metastatic disease (HR=0.41, 95% CI=0.25-0.67, P=0.0004) and older age (HR=0.94 per 5 years, 95% CI=0.90-0.99, P=0.01) were significant predictors of improved OS. Progression of disease during first-line treatment (HR=1.24, 95% CI=0.96-1.59) or within the first 3 months of completion of first-line treatment (HR=1.42, 95% CI=1.09-1.83) were predictors of an increased risk of death compared with progression between 3 and 6 months (P=0.03). Health-related quality of life outcomes were reported in only one of the three trials, precluding meta-analysis of these parameters.
  
  
  CONCLUSIONS
  This meta-analysis of patient-level data confirms that second-line chemotherapy treatment results in significantly better OS compared with SC alone in patients with platinum and fluoropyrimidine refractory gastric and oesphageal adenocarcinoma. Health-related quality of life outcomes should be included in future trials in this setting.
authors.affiliation: Department of Oncology, Addenbrooke's Hospital, Box 193, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Tobias
authors.initials: T
authors.lastname: Janowitz
authors.affiliation: Charité-Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Thuss-Patience
authors.affiliation: Warwick Medical School Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Marshall
authors.affiliation: Department of Internal Medicine, School of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea.
authors.forename: Jung Hun
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Oncology, Addenbrooke's Hospital, Box 193, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Connell
authors.affiliation: Department of Oncology, Addenbrooke's Hospital, Box 193, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Cook
authors.affiliation: Charité-Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Augustenburger Platz 1, 13353 Berlin, Germany.|Warwick Medical School Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Dunn
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University Samsung Medical Center, Seoul 135-710, South Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Oncology, Addenbrooke's Hospital, Box 193, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Hugo
authors.initials: H
authors.lastname: Ford
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000628:therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000628:therapy*; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic