Chemotherapy versus 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 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 TM for phase 3 clinical trials that compared second line chemotherapy with supportive care 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. 154 patients received single agent docetaxel and 84 patients single agent irinotecan, each with supportive care. Supportive care alone was given to 172 patients. Chemotherapy significantly reduced the risk of death (HR=0.63, 95% 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% 0.36-0.67, p<0.001). Overall survival benefit was greatest for patients who prog ressed 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 overall survival. 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 (HRQoL) outcomes were reported in only one of the three trials, precluding meta-analysis of these parameters.

CONCLUSION This meta-analysis of patient level data confirms that second line chemotherapy treatment results in significantly better overall survival co mpared with supportive care alone in patients with platinum and fluoropyrimidine refract ory gastric and oesphageal adenocarcinoma. HRQoL outcomes should be included in future trials in this setting.