Abstract
ABSTRACT Background The correlation between progression-free survival (PFS) or time to progression (TTP) and overall survival (OS) has been evaluated in patients with advanced gastric cancer (AGC) who received first-line chemotherapy (Shitara, K et al. Invest New Drug 2011; Shitara K and Burzykowski T, et al, ASCO 2011). However, no corresponding analysis had been done in patients who underwent second-line chemotherapy for AGC. Methods We evaluated the potential of PFS, TTP, response rate (RR), or disease control rate (DCR) to act as surrogates for OS in phase II and III trials of second-line chemotherapy for AGC by comprehensive literature-based analysis. Correlations between each end point and OS were evaluated by Spearman rank correlation coefficient (r). Subgroup analyses were also conducted. Results Fifty-six trials, including four randomized studies, were selected for analysis and covered a total of 61 treatment arms and 3038 patients; 34 studies were conducted in Asia, 20 studies in Non-Asian countries, and two studies in both regions. Median PFS/TTP and OS showed a moderate correlation with r of 0.51 (95% CI, 0.31–0.73). Correlation tended to be higher in PFS (r = 0.62) than TTP (r = 0.29) and higher in non-Asian trials (r = 0.73) than Asian trials (r = 0.32). Correlation between PFS/TTP and OS among the trials in which eligibility required failure to previous fluorouracil and cisplatin also showed low correlation (r = 0.48). The RR and DCR also did not show high correlation with OS (r = 0.30; 95% CI 0.04–0.56; r = 0.53; 95% CI 0.31–0.75). The hazard ratio (HR) of PFS and OS in each arms of the four randomized studies showed a low correlation with an r of 0.10. Conclusion Our results indicate that PFS/TTP, RR, and DCR did not correlate sufficiently with OS to be used as surrogate end points in patients with AGC who underwent second-line chemotherapy. Further research is needed based on individual patient data from ongoing randomized trials.
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