Combined analysis of three randomized phase III trials comparing S-1 monotherapy and S-1 combination therapy for first-line treatment of advanced gastric cancer.

Abstract

49 Background: S-1 is the gold standard for first line therapy of advanced gastric cancer in Asia. There have been multiple meta-analyses published researching and comparing the efficacy and safety of S-1 monotherapy versus combination1,2. However there has been no analysis using actual trial data. Methods: Actual data from three randomized Phase III trials were combined to compare the efficacy of S-1 Monotherapy and S-1 combination therapy. The START trial, comparing S-1 and combination S-1 with docetaxel, SPIRITS, comparing S-1 and combination S-1 with cisplatin and TOP-002, comparing S-1 and S-1 combination with irinotecan, were merged and combined. For this analysis, the three S-1 arms were combined (n = 642) and the different S-1 combination therapy were combined (n = 617) creating two new treatment arms. The primary efficacy outcome of overall survival, progression free survival and subset analysis of overall survival stratified by baseline characteristics were performed. Results: A total of 1248 patients, including 210 Korean patients from the START were used in the analysis. The median overall survival days for S-1 combination and monotherapy was 382 [209, 648] and 321 [177, 597] and median progression free survival days for S-1 combination and monotherapy was 153 [81, 267] and 122 [61, 204]. Both overall survival (p = 0.0088 HR = 0.85 (0.76,0.96)) and progression free survival ( p = < 0.001 HR = 0.75 (0.67,0.85)) was significantly longer in the combination therapy arm compared to the monotherapy arm. Conclusions:Although there are limitations, the analysis re-confirms that S-1 combination therapy shows to be more efficacious compared to S-1 monotherapy for advanced gastric cancer patients. It must be noted that heterogeneity of the S-1 arm was not carefully considered when combining the S-1 data for the trials. In addition, the results are limited to the Asian (Japanese and Korean) population.