Advanced colorectal cancer subtypes (aCRCS) help select oxaliplatin-based or irinotecan-based therapy for colorectal cancer

Shin Takahashi, Yasuhiro Sakamoto, Tadamichi Denda, Atsuo Takashima, Yoshito Komatsu, Masato Nakamura, Hisatsugu Ohori, Tatsuro Yamaguchi, Yoshimitsu Kobayashi, Hideo Baba, Masanori Kotake, Kenji Amagai, Hitoshi Kondo, Ken Shimada, Atsushi Sato, Satoshi Yuki, Akira Okita, Kota Ouchi, Keigo Komine, Mika WatanabeSatoshi Morita, Chikashi Ishioka

Research output: Contribution to journalArticlepeer-review

Abstract

Oxaliplatin (OX) and irinotecan (IRI) are used as key drugs for the first-line treatment of metastatic colorectal cancer (mCRC). However, no biomarkers have been identified to decide which of the drugs is initially used. In this translational research (TR) of the TRICOLORE trial, the advanced colorectal cancer subtype (aCRCS) was analyzed as a potential biomarker for the selection of OX or IRI. We collected 335 (68.8%) formalin-fixed, paraffin-embedded (FFPE) primary tumor specimens from 487 patients registered in the TRICOLORE trial and performed direct sequencing and immunohistochemical staining of CRC-related genes, comprehensive gene-expression analysis, and genome-wide methylation analysis. The progression-free survival (PFS) of the IRI group was significantly better compared with the OX group in BRAF wild-type (WT), PTEN-positive, and aCRCS A1 patients. Among the molecular factors, aCRCS were only associated with the PFS of OX and IRI groups. The PFS of the IRI group was significantly better compared with the OX group in aCRCS A1 + B1 (hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.41-0.82; P =.0023). In contrast, the OX group had better PFS compared with the IRI group in aCRCS B2, although this was not statistically significant (HR = 1.66; 95% CI = 0.94-2.96; P =.083). Nearly half of patients with mCRC (46.8%, aCRCS A1 + B1) respond well to IRI, while only about 18.5% (aCRCS B2) of patients with mCRC responded well to OX. In conclusion, the aCRCS might be a predictive factor for the clinical outcomes of OX-based and IRI-based therapies.

Original languageEnglish
Pages (from-to)1567-1578
Number of pages12
JournalCancer science
Volume112
Issue number4
DOIs
Publication statusPublished - 2021 Apr

Keywords

  • TRICOLORE
  • aCRCS
  • irinotecan
  • oxaliplatin
  • predictive biomarker

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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