Molecular Biomarker Study in a Randomised Phase III Trial of Irinotecan Plus S-1 versus S-1 for Advanced Gastric Cancer (GC0301/TOP-002)

作者：Tsuburaya A^*; Sugimoto N; Imamura H; Nishikawa K; Imamoto H; Tsujinaka T; Esaki T; Horita Y; Kimura Y; Fujiya T; Takayama O; Oono R; Yabusaki H; Taguri M; Morita S; Yamada Y; Tan P; Ninomiya M; Furukawa H; Sasako M

来源：Clinical Oncology, 2016, 28(8): E45-E51.

DOI：10.1016/j.clon.2016.04.001

• Excision repair cross-complementing gene 1
• gastric cancer
• irinotecan
• predictive factor
• thymidine phosphorylase
• thymidylate synthase

Aims: Gastric cancer is a common and heterogeneous disease; however, global standard and biomarkers for selecting chemotherapy regimens have not been established. This study was designed retrospectively to identify molecular biomarkers for irinotecan plus S-1 (IRI-S) and S-1 therapy from subset analyses in GC0301/TOP-002, a randomised phase III trial for advanced gastric cancer.
Materials and methods: Paraffin-embedded primary tumour specimens were collected from 126 of 326 randomised patients in GC0301/TOP-002. The mRNA was measured for thymidylate synthase, dihydropyrimidine dehydrogenase, topoisomerase I, excision repair cross-complementing gene 1 (ERCC1) and thymidine phosphorylase; categorised into low and high to analyse their association with efficacy end points.
Results: There was no significant difference in each mRNA between S-1 and IRI-S groups, whereas there were differences among some clinical characteristics. Multivariate analyses for overall survival showed that mRNA levels were not correlated with prognosis. By comparison, between IRI-S and S-1 arms, low thymidylate synthase, low ERCC1 and high thymidine phosphorylase were associated with better prognosis for IRI-S versus S-1 (hazard ratio = 0.653, 0.702 and 0.709, respectively; P < 0.15 for each interaction).
Conclusion: Low thymidylate synthase, low ERCC1 and high thymidine phosphorylase are candidates for predictive biomarkers for first-line treatment in advanced gastric cancer by IRI-S. Further study is warranted to confirm these results in other clinical trials and cohort studies.

• 出版日期2016-8