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
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 se...
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Nature Publishing Group
2025-05-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02229-4 |
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| author | Yuankai Shi Yi Ba Junye Wang Jianping Xiong Kangsheng Gu Yigui Chen Zhendong Zheng Zishu Wang Weijian Guo Ying Cheng Xianli Yin Yunpeng Liu Yuxian Bai Enxiao Li Qi Li Liangjun Zhu Wei Li Da Jiang Jingdong He Jiansi Chen Jianguo Sun Sheng Hou |
| author_facet | Yuankai Shi Yi Ba Junye Wang Jianping Xiong Kangsheng Gu Yigui Chen Zhendong Zheng Zishu Wang Weijian Guo Ying Cheng Xianli Yin Yunpeng Liu Yuxian Bai Enxiao Li Qi Li Liangjun Zhu Wei Li Da Jiang Jingdong He Jiansi Chen Jianguo Sun Sheng Hou |
| author_sort | Yuankai Shi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-50ab62ced87e43a1b25dac625badba01 |
| institution | DOAJ |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Publishing Group |
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| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-50ab62ced87e43a1b25dac625badba012025-08-20T03:09:21ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-05-011011910.1038/s41392-025-02229-4First-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 trialYuankai Shi0Yi Ba1Junye Wang2Jianping Xiong3Kangsheng Gu4Yigui Chen5Zhendong Zheng6Zishu Wang7Weijian Guo8Ying Cheng9Xianli Yin10Yunpeng Liu11Yuxian Bai12Enxiao Li13Qi Li14Liangjun Zhu15Wei Li16Da Jiang17Jingdong He18Jiansi Chen19Jianguo Sun20Sheng Hou21National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted DrugsPeking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeAffiliated Hospital of Jining Medical UniversityThe First Affiliated Hospital of Nanchang UniversityThe First Affiliated Hospital of Anhui Medical UniversityFujian Cancer HospitalGeneral Hospital of Northern Theater CommandThe First Affiliated Hospital of Bengbu Medical CollegeFudan University Shanghai Cancer CenterJilin Cancer HospitalHunan Cancer HospitalThe First Hospital of China Medical UniversityHarbin Medical University Cancer HospitalThe First Affiliated Hospital of Xi’an Jiaotong UniversityShanghai General HospitalJiangsu Cancer HospitalThe First Hospital of Jilin UniversityThe Fourth Hospital of Hebei Medical UniversityHuai’an First People’s HospitalAffiliated Tumor Hospital of Guangxi Medical UniversityThe Second Affiliated Hospital of Army Medical UniversityState Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, Taizhou Mabtech Pharmaceutical Co. LtdAbstract 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.https://doi.org/10.1038/s41392-025-02229-4 |
| spellingShingle | Yuankai Shi Yi Ba Junye Wang Jianping Xiong Kangsheng Gu Yigui Chen Zhendong Zheng Zishu Wang Weijian Guo Ying Cheng Xianli Yin Yunpeng Liu Yuxian Bai Enxiao Li Qi Li Liangjun Zhu Wei Li Da Jiang Jingdong He Jiansi Chen Jianguo Sun Sheng Hou 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 Signal Transduction and Targeted Therapy |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://doi.org/10.1038/s41392-025-02229-4 |
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