@article{00b0d7bee7664372bc287230187bd645,
title = "Advanced colorectal cancer subtypes (aCRCS) help select oxaliplatin-based or irinotecan-based therapy for colorectal cancer",
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.",
keywords = "TRICOLORE, aCRCS, irinotecan, oxaliplatin, predictive biomarker",
author = "Shin Takahashi and Yasuhiro Sakamoto and Tadamichi Denda and Atsuo Takashima and Yoshito Komatsu and Masato Nakamura and Hisatsugu Ohori and Tatsuro Yamaguchi and Yoshimitsu Kobayashi and Hideo Baba and Masanori Kotake and Kenji Amagai and Hitoshi Kondo and Ken Shimada and Atsushi Sato and Satoshi Yuki and Akira Okita and Kota Ouchi and Keigo Komine and Mika Watanabe and Satoshi Morita and Chikashi Ishioka",
note = "Funding Information: ST has received honoraria from Taiho and Asahi Kasei and research grants from Merck Biopharma and Ono. TD has received honoraria from Sawai and Sysmex and research grants from Taiho, MSD, and Ono. AT has received honoraria from Chugai, Takeda, Eli Lilly, Ono, Taiho, and Sanofi, and research grants from Ono, MSD, Sumitomo Dainippon, Taiho, and Takeda. YK has received honoraria from Asahi Kasei, EA Pharma, MSD, Otsuka, Ono, Shiseido, Yakult, Kyowa Kirin, Sanofi, Sawai, Shire, Daiichi Sankyo, Taiho, Takeda, Mitsubishi Tanabe, Chugai, Nipro, Eli Lilly, Nippon‐Kayaku, Bayer, Pfizer, Bristol‐Myers Squibb, Merck Biopharma, and Novartis, and research grants from Takeda, Shionogi, Ono, Taiho, Chugai, Asahi Kasei, Kyowa Kirin, Nippon Zoki, Eli Lilly, and Daiichi Sankyo. MN has received honoraria from Chugai, Taiho, Merck Biopharma, Takeda, Ono, Eli Lilly, Otsuka, Yakult, Sanofi, and Bayer. TY has received honoraria from Chugai and Taiho. HB has received honoraria from Eli Lilly, Taiho, Ono, Chugai, and Takeda and research funds from Ono, Merck Biopharma, MSD, and Taiho and research grants from Taiho, Yakult, and Chugai. KS has received honoraria from Taiho, Chugai, and Daiichi Sankyo. AS has received honoraria from Taiho, Chugai, Daiichi Sankyo, Eli Lilly, and Ono. SY has received honoraria from Chugai, Takeda, and Bristol‐Myers. SM has received honoraria from AstraZeneca, Bristol‐Myers Squibb, Chugai, Eli Lilly, MSD, Boehringer Ingelheim, Ono, Pfizer, and Taiho, and research grants from Boehringer Ingelheim. CI has received research grants from Hitachi, Chugai, Taiho, Ono, Eisai, Taleda, Asahi Kasei, and Daiichi Sankyo. All remaining authors declare no conflict of interest. Funding Information: We thank our patients and medical and technical staff, especially Ms Hiromi Nakano. A list of participating institutions to TR is given in the Appendix S2 . This work was supported by the Tokyo Cooperative Oncology Group with funding from Taiho Pharmaceutical Co. Ltd., Japan [no grant number] under the study contract, and partly supported by a grant from the Project for Development of Innovative Research on Cancer Therapeutics (P‐DIRECT) [grant number 11110018] and the Project for Cancer Research and Therapeutic Evolution (P‐CREATE) [grant number 16770660] by the Japan Agency for Medical Research and Development. Publisher Copyright: {\textcopyright} 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",
year = "2021",
month = apr,
doi = "10.1111/cas.14841",
language = "English",
volume = "112",
pages = "1567--1578",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "4",
}
