Efficacy and safety of cetuximab-irinotecan rechallenge versus regorafenib in ras wild-type metastatic colorectal cancer: a single-center exploratory randomized trial.

Authors

Hao Chen, Tao Jiang, Han Wang, Jianwei Zheng, Bin Du, Xiaojiao Weng, Na Yao, Yingjiao Zhu, Qing Liu, Fangyu Lin, Xinli Wang, Xiaoyan Lin

Published in

BMC cancer. Jul 21, 2026. Epub Jul 21, 2026.

Abstract

Anti-epidermal growth factor receptor (EGFR) antibodies are widely used in the treatment of RAS wild-type metastatic colorectal cancer (mCRC) across various lines of therapy, including after disease progression. However, evidence from randomized controlled trials regarding the efficacy of cetuximab rechallenge in patients who initially responded to prior cetuximab but subsequently progressed after a cetuximab-free interval remains limited.
This single-center, prospective, exploratory randomized trial (ChiCTR1900026961) evaluated cetuximab plus irinotecan rechallenge versus regorafenib in patients with RAS wild-type, microsatellite-stable mCRC who had previously responded to then progressed off cetuximab. Progression-free survival (PFS) was the primary endpoint, with overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety as secondary endpoints. Univariate and multivariate Cox regression analyses were performed to identify potential prognostic factors, and an exploratory nomogram was developed for hypothesis generation.
Among 68 randomized patients, cetuximab plus irinotecan rechallenge was associated with longer median PFS and OS than regorafenib. The DCR and ORR were numerically higher in the rechallenge group. Median PFS was 5.5 months versus 2.6 months, and median OS was 18.8 months versus 10.4 months. Adverse events in the cetuximab group were predominantly grade 1-2 and manageable with supportive care. Univariate and multivariate analyses identified age, ECOG status, and cetuximab-free interval as potential prognostic factors. An exploratory nomogram was constructed based on these factors.
These findings suggest that cetuximab plus irinotecan rechallenge may be associated with clinical benefit and acceptable toxicity in selected patients with RAS/BRAF wild-type mCRC. The exploratory nomogram requires further validation. These results support further investigation of rechallenge strategies and biomarker-guided approaches in advanced CRC.
This study was registered with the Chinese Clinical Trial Registry on October 27, 2019 (registration number: ChiCTR1900026961).

PMID:
42477619
Bibliographic data and abstract were imported from PubMed on 21 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.