Gastric cancer biomarker analysis in patients treated with different adjuvant chemotherapy regimens within SAMIT, a phase III randomized controlled trial

Author:

Oshima Takashi,Tsuburaya Akira,Yoshida Kazuhiro,Yoshikawa Takaki,Miyagi Yohei,Rino Yasushi,Masuda Munetaka,Guan Jia,Tan Patrick,Grabsch Heike I.,Sakamoto Junichi,Tanaka Shiro

Abstract

AbstractBiomarkers for selecting gastric cancer (GC) patients likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy (sequential paclitaxel) were investigated using tissue samples of patients recruited into SAMIT, a phase III randomized controlled trial. Total RNA was extracted from 556 GC resection samples. The expression of 105 genes was quantified using real-time PCR. Genes predicting the benefit of sequential paclitaxel on overall survival, disease-free survival, and cumulative incidence of relapse were identified based on the ranking of p-values associated with the interaction between the biomarker and sequential paclitaxel or monotherapy groups. Low VSNL1 and CD44 expression predicted the benefit of sequential paclitaxel treatment for all three endpoints. Patients with combined low expression of both genes benefitted most from sequential paclitaxel therapy (hazard ratio = 0.48 [95% confidence interval, 0.30–0.78]; p < 0.01; interaction p-value < 0.01). This is the first study to identify VSNL1 and CD44 RNA expression levels as biomarkers for selecting GC patients that are likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy. Our findings may facilitate clinical trials on biomarker-oriented postoperative adjuvant chemotherapy for patients with locally advanced GC.

Funder

JSPS KAKENHI

Epidemiological and Clinical Research Information Network

Kanagawa Standard Anti-Cancer Therapy Support System

Japan Agency for Medical Research and Development

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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