Combination therapy of bevacizumab with either S-1 and irinotecan or mFOLFOX6/CapeOX as first-line treatment of metastatic colorectal cancer (TRICOLORE): Exploratory analysis of RAS status and primary tumour location in a randomised, open-label, phase III, non-inferiority trial.

Abstract

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.

• Authors: Tadamichi Denda, Atsuo Takashima, Makio Gamoh, Ichiro Iwanaga, Yoshito Komatsu, Masanobu Takahashi, Masato Nakamura, Hisatsugu Ohori, Akiko Sakashita, Masahiro Tsuda, Yoshimitsu Kobayashi, Hideo Baba, Masanori Kotake, Chikashi Ishioka, Yasuhide Yamada, Atsushi Sato, Satoshi Yuki, Satoshi Morita, Shin Takahashi, Tatsuro Yamaguchi, Ken Shimada
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 154 Pg. 296-306 (09 2021) ISSN: 1879-0852 [Electronic] England
• PMID: 34304054 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Drug Combinations
• Organoplatinum Compounds
• S 1 (combination)
• Tegafur
• Bevacizumab
• Oxonic Acid
• Irinotecan
• Proto-Oncogene Proteins B-raf
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bevacizumab (administration & dosage)
• Colorectal Neoplasms (drug therapy, genetics, mortality, pathology)
• Drug Combinations
• Female
• Fluorouracil (therapeutic use)
• Genes, ras
• Humans
• Irinotecan (administration & dosage)
• Leucovorin (therapeutic use)
• Male
• Middle Aged
• Mutation
• Neoplasm Metastasis
• Organoplatinum Compounds (therapeutic use)
• Oxonic Acid (administration & dosage)
• Proto-Oncogene Proteins B-raf (genetics)
• Quality of Life
• Tegafur (administration & dosage)