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

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.