Prognostic and predictive factors for overall survival in metastatic oesophagogastric cancer: A systematic review and meta-analysis

Abstract

Background: Consistent evidence on prognostic and predictive factors for advanced oesophagogastric cancer is lacking. Therefore, we performed a systematic review and meta-analysis. Methods: We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) databases for phase II/III randomised controlled trials (RCTs) until February 2017 on palliative systemic therapy for advanced oesophagogastric cancer that reported prognostic or predictive factors for overall survival (PROSPERO-CRD42014015177). Prognostic factors were identified from multivariate regression analyses in study reports. Factors were considered potentially clinically relevant if statistically significant (P ≤ 0.05) in multivariate analysis in ≥50% of the total number of patients in the pooled sample of the RCTs and were reported with a pooled sample size of ≥600 patients in the first-line or ≥300 patients in the beyond first-line setting. Predictive factors were identified from time-to-event stratified treatment comparisons and deemed potentially clinically relevant if the P-value for interaction between subgroups was ≤0.20 and the hazard ratio in one of the subgroups was significant (P ≤ 0.05). Results: Forty-six original RCTs were included (n = 15,392 patients) reporting on first-line (n = 33) and beyond first-line therapy (n = 13). Seventeen prognostic factors for overall survival in the first-line and four in the beyond first-line treatment setting were potentially clinically relevant. Twenty-one predictive factors in first-line and nine in beyond first-line treatment setting were potentially relevant regarding treatment efficacy. Conclusions: The prognostic and predictive factors identified in this systematic review can be used to characterise patients in clinical practice, be included in future trial designs, enrich prognostic tools and generate hypotheses to be tested in future research to promote patient-centred treatment.