Individual patient data-based meta-analysis assessing pre-operative chemotherapy in resectable oesophageal carcinoma

Abstract

4512 Background: Optimal management of operable localised oesophageal carcinoma remains to be determined. The debate is fuelled by some positive individual trials showing a benefit of preoperative chemotherapy (CT+S) or preoperative chemo-radiotherapy (CRT+S) over surgery alone (S). Our group has initiated an individual patient data-based meta-analysis to quantify the potential benefit of CT+S over S. Methods: The methodology used for trial identification and data analysis has been previously reported. The primary endpoint was overall survival (OS). The secondary endpoints were disease-free-survival (DFS) analyzed with a 6 months landmark method, tumour resectability (complete resection rate) and post-operative mortality. The logrank-test, stratified by trial, and hazard ratio (HR) were used for comparison. Subgroup analyses by age, sex, performance status, and histologic type were prospectively planned. Results: Twelve eligible randomized trials (2,284 patients) were identified. Individual patient data from 9 trials (2,102 patients) with a median follow-up of 5.3 years were available for the OS analysis. There was a statistically significant OS benefit in favour of CT+S (HR=0.87, 95% CI 0.79–0.95, p=0.003) translating into a 5-year absolute OS increase of 4% (from 16 to 20%). Based on 7 trials (1,849 patients), the HR for DFS was 0.82 (95% CI 0.74–0.91, p=0.001) in favour of CT+S, representing a 5-year absolute DFS benefit of 4% (from 6 to 10%). The complete resection rate across 8 trials (1,933 patients) was significantly greater in the CT+S arm (67%) compared to the S arm (62%) (OR=0.81, 95% CI 0.67–0.98, p=0.03). No difference was seen in postoperative death (6.7%). No interaction between treatment effect and patients characteristics was seen. Conclusions: Individual patient data-based meta-analysis represents the highest level of evidence and this study shows a small but significant overall and disease-free survival benefit in favour of preoperative chemotherapy over surgery alone. Unrestricted grants from LNCC and Sanofi-Aventis. No significant financial relationships to disclose.