ISY10-4 - Development of new agents for unresectable gastric cancer: Global? Asian? Japanese?

Abstract

Many clinical trials with new drugs for unresectable gastric cancer has been globally conducted. Although barriers in global development from investigators' point of view do exist, some were overcome and some have been still issues. Drug-specific issues should be considered such as pharmacogenomics evaluation. For example, in Asian populations where the frequency of UGT1A1*28 is low, other UGT1A1 variants can also play a role in irinotecan toxicity: in a Japanese study, two haplotype (*28 containing the UGT1A1*28 allele and *6 containing the exon 1 G71R polymorphism) groups were associated with reduced area under the curve (AUC) ratios of SN-38G to SN-38, which is predicted to have an effect on irinotecan toxicity. Patients with one *6 haplotype and one *28 haplotype had significantly lower AUC ratios compared with patients with homozygous wild-type UGT1A1. Difference in clinical practice has been a common problem when planning global studies. In AVAGAST study, which compared XP vs XP+bevacizumab in the 1st-line setting, HR in OS was 0.63 in Pan-America and 0.97 in Asia. These differences may come from the differences in proportion of 2nd-line treatment and proportion of minimal peritoneal metastasis. Such experiences have been utilized into planning and conducting subsequent global trials in gastric cancer. On the other hand, in Asia, especially in Japan, specific development for patients with peritoneal metastasis have been conducted. Now, however, only patients with severe peritoneal metastasis are excluded from the standard development strategy, there are no conflicts with global development. Totally, Asian trials can be performed without difficulties, and there are some issues to consider to plan and conduct global trials.