First-line treatment of anti-EGFR monoclonal antibody cetuximab β plus FOLFIRI versus FOLFIRI alone in Chinese patients with RAS/BRAF wild-type metastatic colorectal cancer: a randomized, phase 3 trial

Cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) represents a first-line therapeutic standard for RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients. Despite this established approach, cetuximab β (CMAB009), as a modified antibody of cetuximab, prospectively selected for dual RAS/BRAF wild-type patients, has not yet been validated in the Chinese mCRC patients through phase 3 trial. In this study (ClinicalTrials.gov identifier: NCT03206151), patients with RAS/BRAF wild-type mCRC who were not suitable for radical resection were randomly assigned in a 1:1 ratio to receive cetuximab β plus FOLFIRI or FOLFIRI alone. The primary endpoint was blinded independent review committee-assessed progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), surgery rate for metastasis and R0 resection rate, and safety. From January 4, 2018 to September 2, 2021, a total of 505 eligible patients were enrolled and received study treatment; the median follow-up duration was 8.7 months (95% confidence interval [CI], 7.77 to 9.29) and 5.9 months (95% CI, 5.63 to 6.65) in cetuximab β plus FOLFIRI group and FOLFIRI group, respectively. Compared to FOLFIRI alone, cetuximab β plus FOLFIRI demonstrated statistically significant improvements in median PFS (13.1 vs. 9.6 months, hazard ratio [HR], 0.639; 95% CI, 0.468 to 0.872; P = 0.004), median OS (28.3 vs. 23.1 months, HR, 0.729; 95% CI, 0.551 to 0.965; P = 0.024), and ORR (69.1% vs. 42.3%, odds ratio, 3.090; 95% CI, 2.280 to 4.189; P < 0.001). Cetuximab β plus FOLFIRI exhibited manageable toxicity without novel safety signals. This study demonstrated that cetuximab β plus FOLFIRI provided significant clinical benefits as a first-line treatment for patients with RAS/BRAF wild-type mCRC. Compared to FOLFIRI alone, cetuximab β plus FOLFIRI therapy led to prolonged median PFS and OS while maintaining a manageable safety profile, offering a new treatment option for this patient population.

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Publication Details

Journal
Signal Transduction and Targeted Therapy
Published
2025-05-06
DOI
https://doi.org/10.1038/s41392-025-02229-4
Citations
6
Primary Topic
Colorectal Cancer Treatments and Studies
Type
article
Field-Weighted Citation Impact
6.27

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article

First-line treatment of anti-EGFR monoclonal antibody cetuximab β plus FOLFIRI versus FOLFIRI alone in Chinese patients with RAS/BRAF wild-type metastatic colorectal cancer: a randomized, phase 3 trial

Junye Wang, Xinbao Yin, Liangjun Zhu, Yi Ba et al.
6 citations
Signal Transduction and Targeted Therapy
Colorectal Cancer Treatments and Studies
6.27
article

First-line treatment of anti-EGFR monoclonal antibody cetuximab β plus FOLFIRI versus FOLFIRI alone in Chinese patients with RAS/BRAF wild-type metastatic colorectal cancer: a randomized, phase 3 trial

Junye Wang, Xinbao Yin, Liangjun Zhu, Yi Ba, Zishu Wang, Ying Cheng, Jiansi Chen, Jianping Xiong, Da Jiang, Yigui Chen, Sheng Hou, Qi Li, Yuxian Bai, Wei Li, Yuankai Shi, Kangsheng Gu, Weijian Guo, Jingdong He, Jianguo Sun, Enxiao Li, Zhendong Zheng, Yunpeng Liu
article en
6 citations

Abstract

Cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) represents a first-line therapeutic standard for RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients. Despite this established approach, cetuximab β (CMAB009), as a modified antibody of cetuximab, prospectively selected for dual RAS/BRAF wild-type patients, has not yet been validated in the Chinese mCRC patients through phase 3 trial. In this study (ClinicalTrials.gov identifier: NCT03206151), patients with RAS/BRAF wild-type mCRC who were not suitable for radical resection were randomly assigned in a 1:1 ratio to receive cetuximab β plus FOLFIRI or FOLFIRI alone. The primary endpoint was blinded independent review committee-assessed progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), surgery rate for metastasis and R0 resection rate, and safety. From January 4, 2018 to September 2, 2021, a total of 505 eligible patients were enrolled and received study treatment; the median follow-up duration was 8.7 months (95% confidence interval [CI], 7.77 to 9.29) and 5.9 months (95% CI, 5.63 to 6.65) in cetuximab β plus FOLFIRI group and FOLFIRI group, respectively. Compared to FOLFIRI alone, cetuximab β plus FOLFIRI demonstrated statistically significant improvements in median PFS (13.1 vs. 9.6 months, hazard ratio [HR], 0.639; 95% CI, 0.468 to 0.872; P = 0.004), median OS (28.3 vs. 23.1 months, HR, 0.729; 95% CI, 0.551 to 0.965; P = 0.024), and ORR (69.1% vs. 42.3%, odds ratio, 3.090; 95% CI, 2.280 to 4.189; P < 0.001). Cetuximab β plus FOLFIRI exhibited manageable toxicity without novel safety signals. This study demonstrated that cetuximab β plus FOLFIRI provided significant clinical benefits as a first-line treatment for patients with RAS/BRAF wild-type mCRC. Compared to FOLFIRI alone, cetuximab β plus FOLFIRI therapy led to prolonged median PFS and OS while maintaining a manageable safety profile, offering a new treatment option for this patient population.

Signal Transduction and Targeted TherapyVol. 10(1)
Hebei Medical University (CN), Nanchang University (CN), Army Medical University (CN), Harbin Medical University (CN), Bengbu Medical College (CN), Dalian Medical University (CN), Jilin University (CN), Anhui Medical University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking Union Medical College Hospital (CN), Tianjin Medical University Cancer Institute and Hospital (CN), SAIC-GM (China) (CN), Shanghai Stomatological Hospital (CN), Fudan University Shanghai Cancer Center (CN), Second Affiliated Hospital of Chongqing Medical University (CN), Huaian First People’s Hospital (CN), Jilin Province Tumor Hospital (CN), Third Affiliated Hospital of Harbin Medical University (CN), Fourth Hospital of Hebei Medical University (CN), Hunan Cancer Hospital (CN), First Affiliated Hospital of Xi'an Jiaotong University (CN), First Hospital of Jilin University (CN), Jiangsu Cancer Hospital (CN), General Hospital of Shenyang Military Region (CN), First Affiliated Hospital of Anhui Medical University (CN), First Hospital of China Medical University (CN), Fujian Provincial Cancer Hospital (CN), First Affiliated Hospital of Bengbu Medical College (CN), Tumor Hospital of Guangxi Medical University (CN), Affiliated Hospital of Jining Medical University (CN), First Affiliated Hospital of Nanchang University (CN), Taizhou University (CN), Chongqing Medical University (CN), China Medical University (CN)
Chinese Academy of Medical Sciences, Peking Union Medical College
Good health and well-being
Openalex Percentile: Top 3%
Colorectal Cancer Treatments and Studies
6.27
DOIOpen Access PDFOpenAlex
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