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Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma : a meta-analysis of patient-level data

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Janowitz, Tobias, Thuss-Patience, Peter, Marshall, A. (Andrea)‏, Kang, Jung Hun, Connell, Claire, Cook, Natalie, Dunn, Janet A., Park, Se Hoon and Ford, Hugo (2016) Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma : a meta-analysis of patient-level data. British Journal of Cancer, 114 (4). pp. 381-387. doi:10.1038/bjc.2015.452

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Official URL: http://dx.doi.org/10.1038/bjc.2015.452

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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.

Item Type: Journal Article
Divisions: Faculty of Medicine > Warwick Medical School > Health Sciences > Clinical Trials Unit
Faculty of Medicine > Warwick Medical School > Health Sciences
Faculty of Medicine > Warwick Medical School
Journal or Publication Title: British Journal of Cancer
Publisher: Nature Publishing Group
ISSN: 0007-0920
Official Date: 15 February 2016
Dates:
DateEvent
15 February 2016Published
30 November 2015Accepted
24 August 2015Submitted
Volume: 114
Number: 4
Page Range: pp. 381-387
DOI: 10.1038/bjc.2015.452
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
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