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A triplet combination of FOLFOXIRI plus cetuximab as first-line treatment in RAS wild-type, metastatic colorectal cancer: a dose-escalation phase Ib study

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International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

The triplet-agent (5-fluorouracil/leucovorin, oxaliplatin, and irinotecan; FOLFOXIRI) combined with an anti-epidermal growth factor receptor antibody as a first-line treatment of metastatic colorectal cancer (mCRC) has shown promising results in Western trials. This phase Ib study assessed the safety of FOLFOXIRI plus cetuximab in Japanese patients with RAS wild-type mCRC.

Methods

Patients with previously untreated RAS wild-type mCRC received weekly cetuximab (400 mg/m2 at week 1 and subsequently 250 mg/m2) plus FOLFOXIRI that consisted of irinotecan (100, 120, and 150 mg/m2 defined as dose levels 0, 1, and 2), followed by oxaliplatin 85 mg/m2 and l-leucovorin 200 mg/m2 and then 5-fluorouracil 2400 mg/m2. The dose level of irinotecan was escalated starting at dose level 1 in a 3 + 3 manner. The primary endpoint was to determine the maximum-tolerated dose (MTD) and the recommended phase-2 dose (RP2D). Secondary endpoints included safety, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).

Results

Nine patients were enrolled. The MTD was not reached at dose level 2 and the RP2D was 150 mg/m2 irinotecan. The most frequent grade 3/4 adverse events were neutropenia (44%), fatigue (11%), paronychia (22%), and acneiform rash (11%). No dose-limiting toxicities occurred in any of the enrolled patients. No treatment-related death was observed. The ORR was 89% (95% confidence interval 52–100%).

Conclusion

The safety profile of the combination of cetuximab and FOLFOXIRI was acceptable and promising anti-tumor activity was demonstrated, supporting further study in patients with RAS wild-type mCRC.

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Acknowledgements

The authors would like to thank Enago (www.enago.jp) for the English language review.

Funding

This study was conducted with no funding.

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Authors and Affiliations

  1. Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan

    Shigenori Kadowaki, Toshiki Masuishi, Takashi Ura, Keiji Sugiyama, Seiichiro Mitani, Yukiya Narita, Hiroya Taniguchi & Kei Muro

  2. Department of Medical Oncology, Nagoya Medical Center, Nagoya, Aichi, Japan

    Keiji Sugiyama

  3. Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan

    Seiichiro Mitani

  4. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Hiroya Taniguchi

Authors
  1. Shigenori Kadowaki
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  2. Toshiki Masuishi
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  3. Takashi Ura
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  4. Keiji Sugiyama
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  6. Yukiya Narita
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  7. Hiroya Taniguchi
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Corresponding author

Correspondence to Shigenori Kadowaki.

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Conflict of interest

Shigenori Kadowaki received honoraria and research funds from Eli Lilly, Taiho Pharmaceutical Co., and Ono Pharmaceutical Co. and honoraria from Bristol-Myers Squibb, Yakult Honsha Co., Ltd., Chugai Pharmaceutical Co., Ltd., Bayer, and Merck. Toshiki Masuishi received research funds from Daiichi Sankyo, MSD, and Ono Pharmaceutical Co. and honoraria from Taiho Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eli Lilly, Takeda Pharmaceutical Co., Merck, and Bayer. Seiichiro Mitani received honoraria from Taiho Pharmaceutical Co., Eli Lilly, Takeda Pharmaceutical Co., and Ono Pharmaceutical Co. Yukiya Narita received honoraria and research funds from Ono Pharmaceutical Co. and Bristol-Myers Squibb and honoraria from Eli Lilly, Yakult Honsha Co., Daiichi Sankyo, and Taiho Pharmaceutical Co. Hiroya Taniguchi received honoraria and research funds from Takeda Pharmaceutical Co., research funds from Daiichi Sankyo and Sysmex, and honoraria from Taiho Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., and Eli Lilly. Kei Muro received honoraria and research funds from Sanofi; research funds from MSD, Daiichi Sankyo, Sumitomo Dainippon Pharma, Shionogi, Parexel International, Mediscience Planning, and Pfizer; and honoraria from Taiho Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eli Lilly, Takeda Pharmaceutical Co., Ono Pharmaceutical Co., Bayer, and Bristol-Myers Squibb. All remaining authors have no conflicts of interest to declare.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Kadowaki, S., Masuishi, T., Ura, T. et al. A triplet combination of FOLFOXIRI plus cetuximab as first-line treatment in RAS wild-type, metastatic colorectal cancer: a dose-escalation phase Ib study. Int J Clin Oncol 26, 701–707 (2021). https://doi.org/10.1007/s10147-020-01842-3

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  • DOI: https://doi.org/10.1007/s10147-020-01842-3

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