Biomarker analysis to predict the pathological response of locally advanced gastric cancer to neoadjuvant chemotherapy: an exploratory study of the randomized phase II COMPASS trial

Date

10 Oct 2016

Session

Poster display

Presenters

Kazuaki Tanabe

Citation

Annals of Oncology (2016) 27 (6): 15-42. 10.1093/annonc/mdw363

Authors

K. Tanabe1, T. Yoshikawa2, T. Oshima3, Y. Miyagi4, S. Morita5, K. Nishikawa6, Y. Ito7, T. Matsui8, Y. Kimura9, T. Aoyama2, T. Hayashi2, T. Ogata2, H. Cho2, A. Tuburaya10, J. Sakamoto11

Author affiliations

  • 1 Department Of Gastroenterological And Transplant Surgery, Hiroshima University, 7348551 - Hiroshima/JP
  • 2 Department Of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama/JP
  • 3 Department Of Surgery, Yokohama City University Hospital, Yokohama/JP
  • 4 Molecular Pathology & Genetics Division, Kanagawa Cancer Center Research Institute,, Yokohama/JP
  • 5 Department Of Biomedical Statistics And Bioinformatics, Kyoto University-Graduate school of medicine, Kyoto/JP
  • 6 Department Of Surgery, National Hospital Organization Osaka National Hospital, 540-0006 - Osaka/JP
  • 7 Department Of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya/JP
  • 8 Department Of Surgery, Aichi Cancer Center - Aichi Hospital, Okazaki/JP
  • 9 Department Of Surgery, Sakai City Medical Center, Sakai/JP
  • 10 Gastroenterological Center, Yokohama City Medical Center, Yokohama/JP
  • 11 Young Leaders Program, Nagoya University, Graduate School of Medicine, 466-8550 - Nagoya/JP
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Background

The COMPASS trial is a randomized, phase II study to compare two and four courses of neoadjuvant chemotherapy (NAC) with S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) in patients with locally advanced gastric cancer. Among the 83 enrolled patients, the pathological response, defined as regression of the primary tumor by more than one third, was 46% for SC and 26% for PC. The ability to predict the pathological response would greatly facilitate the selection of patients most likely to benefit from NAC as well as those in whom NAC should be continued. We conducted a biomarker study as part of the COMPASS trial to identify predictors of the pathological response to NAC.

Methods

We collected endoscopic biopsy specimens of the primary tumor before NAC. After extraction of mRNA from the paraffin-embedded specimens, the expression levels of 127 genes were quantified by RT-PCR. The relations between gene expression levels and a pathological response of ≥grade 1b were investigated. We studied genes with expression profiles that showed significant interactions with the pathological response to either the SC or PC regimen (P 

Results

Among 83 patients enrolled in the COMPASS trial, mRNA extracted from 80 patients (96.4%) was quantifiable. Interaction analyses showed that TIMP1, RRMI, MUC2, DSG2, EGFR, ZDHHCI4, and CLDN18 were significant predictors of the pathological response to NAC with either SC or PC. A marked pathological response to SC was associated with high expression of TIMP1, RRMI, MUC2, and DSG2 and low expression of EGFR, ZDHHCI4, and CLDN18. A marked pathological response to PC was associated with low expression of TIMP1, RRMI, MUC2, and DSG2 and high expression of EGFR, ZDHHCI4, and CLDN18.

Conclusions

The results of an analysis of mRNA in paraffin-embedded endoscopic biopsy specimens obtained from patients with locally advanced gastric cancer could be used to predict the pathological response to neoadjuvant chemotherapy. The expressions of several genes can predict the pathological response to S-1 + cisplatin or paclitaxel + cisplatin.

Clinical trial identification

This trial was registered in the University Hospital Medical Information Network (UMIN) center (ID UMIN00000 2595).

Legal entity responsible for the study

Non-profit organisation Epidemiological & Clinical Research Information Network (ECRIN)

Funding

Non-profit organisation Epidemiological & Clinical Research Information Network (ECRIN)

Disclosure

All authors have declared no conflicts of interest.

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