Among the RCTs included, postoperative adjuvant chemotherapy based on fluorouracil regimens was associated with reduced risk of death in gastric cancer compared with surgery alone.

4539 Background: Despite potentially curative resection of stomach cancer, 50%-90% of patients die of disease relapse. Numerous randomized clinical trials (RCTs) compared surgery alone (S) to adjuvant chemotherapy (S+CT), but definitive evidence is lacking. Our group has initiated an individual patient data (IPD)-based meta-analysis of all RCTs in the adjuvant gastric setting to quantify the potential benefit of S+CT over S, to study the role of various prognostic factors and their potential interactions with treatments. Methods: All RCTs closed to accrual at the end of 2003 were eligible. Trials with radiotherapy, intraperitoneal chemotherapy, or immunotherapy were excluded. The primary endpoint was OS, the secondary endpoint DFS. Baselines variables included age, sex, tumour size (T) and stage, type of resection (D0, D1, D2 or more), performance status (PS) and geographic area. The Logrank test was stratified by trial and treatment arm. Interaction with treatment was explored with Cox model stratified on trial. No multivariate analysis was performed due to the numerous missing data. Results: Thirty-one eligible RCTs (6,613 patients) were identified. As of December 2008, IPD were available from 16 trials (3,710 patients) with a median follow-up exceeding 8 years. OS benefit was significantly in favour of CT (HR=0.83, 95% CI 0.76–0.91, p <0.0001) with absolute benefit of 6.3% at 5 years. Were associated with lower survival, older age (>66 vs <50) (HR=1.51, 95%CI= 1.31–1.73), PS2 (HR=1.71, 95%CI=1.35–2.15), higher UICC stage (HR=1.41 per unit 95%CI=1.35–1.46) and T>1 (HR=1.57 per unit, 95%CI=1.47–1.67). There was also a strong geographical influence on prognosis (HR=0.30, 95%CI 0.26–0.34 and HR=1.26, 95%CI 1.13–1.41, respectively in Asia and in the US as compared to Europe). Treatment interactions were not identified for all but the stage. Treatment effect appeared slightly stronger for patients with higher stages (HR for treatment effect from 0.88 in stage I to 0.66 in stage IV). Conclusions: Our interim results show a modest but significant OS benefit in favour of adjuvant CT and confirm the impact of tumour staging as well as age and PS on OS. Asian patients have a much better survival than other patients. No significant financial relationships to disclose.

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e16506 Background: In 2013, the GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research through International Collaboration) evaluated the surrogacy of PFS based on IPD of 4,069 patients from 20 randomized trials of AGC. Treatment effects on PFS and on OS were only moderately correlated, and we could not validate PFS as a surrogate endpoint for OS. More recent trials, with refined inclusion criteria and higher standards for evaluating progression, may allow for a more accurate estimate of the correlation. The 2nd round of the GASTRIC sought to re-evaluate the surrogacy of PFS for OS in AGC. Methods: The GASTRIC database was updated with trials published after 2010 which used RECIST (Response Evaluation Criteria in Solid Tumors). Since the proportional hazards assumption was questionable for PFS, we primarily used mean-time ratio as a treatment effect measure, estimated by using the log-logistic model. Using the meta-analytic approach, correlations between PFS and OS at the individual level (Rindiv), and between treatment effects on PFS and on OS at the trial level (Rtrial), were estimated using Spearman’s rank-correlation and estimation-error-adjusted regression, respectively. Surrogate threshold effect was estimated as well. Results: We analyzed 10,912 patient data (1st round 4,069 patients from 20 trials and 2nd round 6,843 patients from 17 trials). Overall, moderate correlations were found at the individual level (Rindiv = 0.75, 95%CI = 0.75 to 0.76 in Hougaard copula) and at the trial level (Rtrial = 0.77, 95%CI = 0.32 to 1.00), respectively. Surrogate threshold effect was equal to 1.29, i.e., observing 29% increase in mean PFS time would predict a significant increase of the OS time. In the subgroup of patients with measurable disease in the 2nd round dataset (4,866 patients), Rtrial was higher and equal to 0.93 (95%CI = 0.70 to 1.00), with STE equal to 1.21. These results were same for 1st and 2nd line trials. Conclusions: The meta-analysis indicates a strong correlation between treatment effects (expressed as log-mean-ratios) on PFS and OS in patients with measurable disease.