TY - JOUR
T1 - Combination therapy of bevacizumab with either S-1 and irinotecan or mFOLFOX6/CapeOX as first-line treatment of metastatic colorectal cancer (TRICOLORE)
T2 - Exploratory analysis of RAS status and primary tumour location in a randomised, open-label, phase III, non-inferiority trial
AU - Denda, Tadamichi
AU - Takashima, Atsuo
AU - Gamoh, Makio
AU - Iwanaga, Ichiro
AU - Komatsu, Yoshito
AU - Takahashi, Masanobu
AU - Nakamura, Masato
AU - Ohori, Hisatsugu
AU - Sakashita, Akiko
AU - Tsuda, Masahiro
AU - Kobayashi, Yoshimitsu
AU - Baba, Hideo
AU - Kotake, Masanori
AU - Ishioka, Chikashi
AU - Yamada, Yasuhide
AU - Sato, Atsushi
AU - Yuki, Satoshi
AU - Morita, Satoshi
AU - Takahashi, Shin
AU - Yamaguchi, Tatsuro
AU - Shimada, Ken
N1 - Funding Information:
This work was supported by the Tokyo Cooperative Oncology Group with funding from Taiho Pharmaceutical Co. Ltd. , Japan, under a study contract. The funders did not have any involvement in the design of the study; the collection, analysis and interpretation of the data; the writing of the article or the decision to submit the article for publication.
Funding Information:
This work was supported by the Tokyo Cooperative Oncology Group with funding from Taiho Pharmaceutical Co. Ltd., Japan, under a study contract. The funders did not have any involvement in the design of the study; the collection, analysis and interpretation of the data; the writing of the article or the decision to submit the article for publication.The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T.D. has received honoraria from Sawai and Sysmex and has received research funding from Taiho, MSD and Ono. A.T. has received honoraria from Chugai, Takeda, Eli Lilly, Ono, Taiho and Sanofi and has received research funding from Ono, MSD, Sumitomo Dainippon, Taiho and Takeda. Y.K. has received honoraria from Asahi Kasei, EA Pharma, MSD, Otsuka Pharmaceutical Factory, Ono, Shiseido, Yakult Honsha, Kyowa Kirin, Sanofi, Sawai, Shire, Daiichi Sankyo, Taiho, Takeda, Mitsubishi Tanabe, Chugai, Nipro, Eli Lilly, Nippon Kayaku, Bayer, Pfizer, Bristol Myers Squibb and Merck Biopharma and has received research funding from Takeda, Shionogi, Ono, Taiho, Chugai, Asahi Kasei, Kyowa Kirin and Nippon Zoki. M.T. has received honoraria from Taiho, Daiichi Sankyo and Bristol Myers Squibb and has received research funding from Ono. M.N. has received honoraria from Chugai, Taiho, Merck Biopharma, Takeda, Ono, Eli Lilly, Otsuka, Yakult Honsha, Sanofi and Bayer. H.O. has received honoraria from Taiho, Takeda, Merck Biopharma, Chugai, Kyowa Kirin, Mochida, Nippon Kayaku, Eli Lilly, Daiichi Sankyo, Bristol Myers Squibb and Yakult Honsha. H.B. has received honoraria from Taiho and has received research funding from Taiho, Yakult Honsha and Chugai. C.I. has received honoraria from Chugai, Taiho, Ono, Merck Biopharma, Novartis, Asahi Kasei, Sanofi, Nippon Kayaku, Daiichi Sankyo, Takeda, Bayer, Eisai, Eli Lilly, Mundipharma, Teijin, Hitachi, Bristol Myers Squibb, Konica Minolta, Pfizer and Mochida and has received research funding from Hitachi, Riken Genesis, Novartis, Daiichi Sankyo, MSD, Bayer, Bristol Myers Squibb, Kissei, Nippon Kayaku and Linical. Y.Y. has received consulting fees from Janssen, has received honoraria from Taiho, Chugai, Ono, Nippon Kayaku and Bristol Myers Squibb and has received research funding from Daiichi Sankyo and Chugai. A.S. has received honoraria from Taiho, Chugai, Daiichi Sankyo, Eli Lilly and Ono. S.Y. has received honoraria from Chugai, Eli Lilly, Takeda, Bristol Myers Squibb, Bayer, Sanofi, Taiho, Ono, MSD, Yakult Honsha, Merck Biopharma, Medical & Biological Laboratories, Daiichi Sankyo and Sumitomo Dainippon. S.M. has received honoraria from AstraZeneca, Bristol Myers Squibb, Chugai, Eli Lilly, MSD, Boehringer Ingelheim, Ono, Pfizer and Taiho and has received research funding from Boehringer Ingelheim. S.T. has received honoraria from Taiho, Chugai, Asahi Kasei, Bayer, Japan Blood Products Organization, Medicon, Termo, Sanofi, Merck Biopharma, Nippon Kayaku, Takeda and Yakult Honsha and has received research funding from Merck Biopharma and Ono. T.Y. has received honoraria from Chugai and Taiho. K.S. has received research funding from Taiho, Chugai, Daiichi Sankyo, Kyowa Kirin and Terumo. All remaining authors have declared no conflicts of interest.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/9
Y1 - 2021/9
N2 - Aim: The TRICOLORE trial previously demonstrated that S-1 and irinotecan plus bevacizumab was non-inferior, based on progression-free survival (PFS), to 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6)/capecitabine and oxaliplatin (CapeOX) plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer (mCRC). Overall survival (OS) data were immature at the time of the primary analysis. Methods: In total, 487 patients from 53 institutions with previously untreated mCRC were randomly assigned (1:1) to receive either mFOLFOX6/CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; 3- or 4-week regimen). The final OS data were analysed from follow-up data collected until 30th September 2017. Results: With a median follow-up period of 48.7 months, median survival times were 32.6 and 34.3 months (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.72–1.10, P = 0.293) and median PFS durations were 10.8 and 14.0 months in the control and experimental groups, respectively (HR: 0.86, 95% CI: 0.71–1.04, P < 0.0001 for non-inferiority). In patients with left-sided RAS wild-type tumours, median PFS durations were 11.4 and 16.9 months in the control and experimental groups, respectively (HR: 0.68, 95% CI: 0.48–0.96, P = 0.028). Conclusion: S-1 and irinotecan plus bevacizumab resulted in comparable OS and non-inferior PFS with that of mFOLFOX6/CapeOX plus bevacizumab treatment as first-line chemotherapy for patients with mCRC. We recommend the use of S-1 and irinotecan plus bevacizumab as a standard first-line regimen independent of tumour sidedness or RAS status in mCRC. Trial registration: UMIN-CTR: 000007834.
AB - Aim: The TRICOLORE trial previously demonstrated that S-1 and irinotecan plus bevacizumab was non-inferior, based on progression-free survival (PFS), to 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6)/capecitabine and oxaliplatin (CapeOX) plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer (mCRC). Overall survival (OS) data were immature at the time of the primary analysis. Methods: In total, 487 patients from 53 institutions with previously untreated mCRC were randomly assigned (1:1) to receive either mFOLFOX6/CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; 3- or 4-week regimen). The final OS data were analysed from follow-up data collected until 30th September 2017. Results: With a median follow-up period of 48.7 months, median survival times were 32.6 and 34.3 months (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.72–1.10, P = 0.293) and median PFS durations were 10.8 and 14.0 months in the control and experimental groups, respectively (HR: 0.86, 95% CI: 0.71–1.04, P < 0.0001 for non-inferiority). In patients with left-sided RAS wild-type tumours, median PFS durations were 11.4 and 16.9 months in the control and experimental groups, respectively (HR: 0.68, 95% CI: 0.48–0.96, P = 0.028). Conclusion: S-1 and irinotecan plus bevacizumab resulted in comparable OS and non-inferior PFS with that of mFOLFOX6/CapeOX plus bevacizumab treatment as first-line chemotherapy for patients with mCRC. We recommend the use of S-1 and irinotecan plus bevacizumab as a standard first-line regimen independent of tumour sidedness or RAS status in mCRC. Trial registration: UMIN-CTR: 000007834.
KW - FOLFOX
KW - IRIS
KW - SIRB
KW - Sidedness
KW - XELOX
UR - http://www.scopus.com/inward/record.url?scp=85111841804&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111841804&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2021.06.013
DO - 10.1016/j.ejca.2021.06.013
M3 - Article
C2 - 34304054
AN - SCOPUS:85111841804
SN - 0959-8049
VL - 154
SP - 296
EP - 306
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -
