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A randomized controlled trial of surgery and postoperative modified FOLFOX6 versus surgery and perioperative modified FOLFOX6 plus cetuximab in patients with KRAS wild-type resectable colorectal liver metastases: EXPERT study

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Abstract

Purpose

To clarify the efficacy of perioperative chemotherapy for the patients with resectable colorectal liver metastases (CLM), we conducted a multicenter randomized phase III trial to compare surgery followed by postoperative FOLFOX regimen with perioperative FOLFOX regimen plus cetuximab in patients with KRAS wild-type resectable CLM.

Methods

Patients who had KRAS wild-type resectable CLM having one to eight liver nodules without extrahepatic disease were randomly assigned to the postoperative chemotherapy group, wherein up-front hepatectomy was performed followed by 12 cycles of postoperative modified FOLFOX6, and the perioperative chemotherapy group (experimental), wherein six cycles of preoperative modified FOLFOX6 plus cetuximab were performed followed by hepatectomy and six cycles of postoperative modified FOLFOX6 plus cetuximab. The primary endpoint was progression-free survival (PFS).

Results

There were 37 patients in postoperative chemotherapy group and 40 patients in the perioperative chemotherapy group who were analyzed. Baseline characteristics were well-balanced between groups. The PFS and overall survival (OS) showed no significant difference (PFS, hazard ratio 1.18 [95% confidence interval 0.69–2.01], P = 0.539: OS, 1.03 [0.46–2.29], P = 0.950). In the postoperative chemotherapy group, 35.1% had a 3-year PFS, and 86.5% had a 3-year OS. Meanwhile, in the perioperative chemotherapy group, 30.0% had a 3-year PFS, and 74.4% had a 3-year OS.

Conclusion

There was no difference in survival found between the group of the perioperative chemotherapy plus cetuximab and that of the postoperative chemotherapy in the cohort of our study. The study was registered in the University Hospital Medical Information Network (UMIN000007787).

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Data availability

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Code Availability

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Acknowledgements

This study was supported by Translational Research Center for Medical Innovation in Kobe, Japan as trial data center. The authors would like to thank Enago (www.enago.jp) for the English language review.

Funding

This study is funded by Translational Research Center for Medical Innovation in Kobe, Japan.

Author information

Authors and Affiliations

  1. Department of Surgery, Graduate School of Medicine, Hepato-Biliary-Pancreatic Surgery Division, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Masaru Matsumura, Kiyoshi Hasegawa, Masaru Oba & Yoshikuni Kawaguchi

  2. Department of Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake Hospital, Tokyo, Japan

    Kensei Yamaguchi

  3. Department of Clinical Research, National Disaster Medical Center, Tokyo, Japan

    Hiroyuki Uetake

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

    Takayuki Yoshino

  5. Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Satoshi Morita

  6. Department of Surgery, Tokyo Metropolitan Health and Hospitals Corporation Ohkubo Hospital, Tokyo, Japan

    Keiichi Takahashi

  7. Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan

    Michiaki Unno

  8. Department of Clinical Oncology, Kochi Health Sciences Center, Kochi, Japan

    Yasuhiro Shimada

  9. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

    Kei Muro

  10. Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan

    Nobuhisa Matsuhashi

  11. Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, and School of Medicine, Tokai University, Isehara, Japan

    Masaki Mori

  12. Department of Gastroenterological Surgery, Graduate School of Medicine, Kumamoto University, Kumamoto, Japan

    Hideo Baba

  13. Department of Digestive and Pediatric Surgery, Graduate School of Medicine, Tokushima University, Tokushima, Japan

    Mitsuo Shimada

  14. Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Yoshihiro Mise & Akio Saiura

  15. Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan

    Tatsuo Kagimura

  16. Department of Surgery, Konan Kosei Hospital, Nagoya, Japan

    Kiyoshi Ishigure

  17. Tokyo Medical and Dental University, Tokyo, Japan

    Kenichi Sugihara

  18. Department of Surgery, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan

    Norihiro Kokudo

Authors
  1. Masaru Matsumura
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  2. Kiyoshi Hasegawa
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Contributions

Study conception and design: KH, MO, KY, HU, TY, S M, KT, MU, YS, KM, MM, HB, MS, AS, KS, and NK. Acquisition of data: MM, KH, MO, KY, HU, TY, KT, MU, YS, KM, NM, MM, HB, MS, YM, YK, TK, KI, AS, and KS. Analysis and interpretation of data: MM, KH, KY, HU, SM, KT, YK, TK, AS, KS, and NK. Drafting of manuscript: MM, YK, and KH. Critical revision of manuscript: KH, MO, KY, HU, TY, SM, KT, MU, YS, KM, MM, HB, MS, YK, AS, KS, and NK.

Corresponding author

Correspondence to Kiyoshi Hasegawa.

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Ethics approval

This study was approved by the institutional ethics committees of the participating institutions and was conducted in accordance with good clinical practice guidelines and the Helsinki Declaration.

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All the patients provided written informed consent.

Consent for publication

Consent for publication was obtained from all the patients.

Conflict of interest

Takayuki Yoshino received lecture fee from Merck biopharma, Japan. All remaining authors declare no competing interests.

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Matsumura, M., Hasegawa, K., Oba, M. et al. A randomized controlled trial of surgery and postoperative modified FOLFOX6 versus surgery and perioperative modified FOLFOX6 plus cetuximab in patients with KRAS wild-type resectable colorectal liver metastases: EXPERT study. Langenbecks Arch Surg 407, 1345–1356 (2022). https://doi.org/10.1007/s00423-022-02434-7

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