FOLFOXIRI plus cetuximab as conversion therapy for unresectable RAS/BRAF wild-type left-sided colorectal cancer with liver-limited metastases: a prospective dual-center pilot study

Wenwei Yang; Dong Chen; Yaru Niu; Guifu Wu; Zhangkan Huang; Xinyu Bi; Hong Zhao; Xu Che; Yongkun Sun

doi:10.3389/fonc.2024.1375906

FOLFOXIRI plus cetuximab as conversion therapy for unresectable RAS/BRAF wild-type left-sided colorectal cancer with liver-limited metastases: a prospective dual-center pilot study

Front Oncol. 2024 Apr 4:14:1375906. doi: 10.3389/fonc.2024.1375906. eCollection 2024.

Authors

Wenwei Yang^#¹, Dong Chen^#², Yaru Niu^#¹, Guifu Wu³, Zhangkan Huang², Xinyu Bi⁴, Hong Zhao⁴, Xu Che^{2

5}, Yongkun Sun¹

Affiliations

¹ Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
³ Department of Medical Oncology, Beijing Chaoyang District Sanhuan Cancer Hospital, Beijing, China.
⁴ Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁵ Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

^# Contributed equally.

Abstract

Purpose: To explore the efficacy and safety of FOLFOXIRI plus cetuximab regimen as conversion therapy for patients with unresectable RAS/BRAF wild-type colorectal liver-limited metastases (CLM).

Patients and methods: This was a dual-center, phase II trial with the rate of no evidence of disease (NED) achieved as the primary endpoint. All enrolled patients with initially unresectable left-sided RAS/BRAF wild-type colorectal liver-limited metastases received a modified FOLFOXIRI plus cetuximab regimen as conversion therapy.

Results: Between October 2019 and October 2021, fifteen patients were enrolled. Nine patients (60%) achieved NED. The overall response rate (ORR) was 92.9%, and the disease control rate (DCR) was 100%. The median relapse-free survival (RFS) was 9 (95% CI: 0-20.7) months. The median progression-free survival (PFS) was 13.0 months (95% CI: 5.7-20.5), and the median overall survival (OS) was not reached. The most frequently occurring grade 3-4 adverse events were neutropenia (20%), peripheral neurotoxicity (13.3%), diarrhea (6.7%), and rash acneiform (6.7%).

Conclusion: The FOLFOXIRI plus cetuximab regimen displayed tolerable toxicity and promising anti-tumor activity in terms of the rate of NED achieved and response rate in patients with initially unresectable left-sided RAS/BRAF wild-type CLM. This regimen merits further investigation.

Keywords: FOLFOXIRI; cetuximab; conversion therapy; liver metastases; metastatic colorectal cancer.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Sanming Project of Medicine in Shenzhen (No. SZSM202011010)and Beijing Bethune Charitable Foundation (No. 2019-052-ZZ).