抗表皮生长因子受体单克隆抗体西妥昔单抗β联合FOLFIRI与单纯FOLFIRI作为中国RAS/BRAF野生型转移性结直肠癌患者一线治疗的随机3期试验。
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.
作者信息
Shi Yuankai, Ba Yi, Wang Junye, Xiong Jianping, Gu Kangsheng, Chen Yigui, Zheng Zhendong, Wang Zishu, Guo Weijian, Cheng Ying, Yin Xianli, Liu Yunpeng, Bai Yuxian, Li Enxiao, Li Qi, Zhu Liangjun, Li Wei, Jiang Da, He Jingdong, Chen Jiansi, Sun Jianguo, Hou Sheng
机构信息
National 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 Drugs, Beijing, PR China.
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
出版信息
Signal Transduct Target Ther. 2025 May 7;10(1):147. doi: 10.1038/s41392-025-02229-4.
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.
西妥昔单抗联合伊立替康、氟尿嘧啶和亚叶酸钙（FOLFIRI）是RAS/BRAF野生型转移性结直肠癌（mCRC）患者的一线治疗标准。尽管有这种既定的治疗方法，但西妥昔单抗β（CMAB009）作为西妥昔单抗的一种改良抗体，前瞻性地选择用于双RAS/BRAF野生型患者，尚未在中国mCRC患者中通过3期试验得到验证。在本研究中（ClinicalTrials.gov标识符：NCT03206151），不适合根治性切除的RAS/BRAF野生型mCRC患者按1:1比例随机分配，接受西妥昔单抗β联合FOLFIRI或单纯FOLFIRI治疗。主要终点是由盲法独立审查委员会评估的无进展生存期（PFS）。次要终点包括总生存期（OS）、客观缓解率（ORR）、疾病控制率（DCR）、转移灶手术率和R0切除率以及安全性。2018年1月4日至2021年9月2日，共有505例符合条件的患者入组并接受研究治疗；西妥昔单抗β联合FOLFIRI组和FOLFIRI组的中位随访时间分别为8.7个月（95%置信区间[CI]，7.77至9.29）和5.9个月（95%CI，5.63至6.65）。与单纯FOLFIRI相比，西妥昔单抗β联合FOLFIRI在中位PFS（13.1个月对9.6个月，风险比[HR]，0.639；95%CI，0.468至0.872；P = 0.004）、中位OS（28.3个月对23.1个月，HR，0.729；95%CI，0.551至0.965；P = 0.024）和ORR（69.1%对42.3%，优势比，3.090；95%CI，2.280至4.189；P < 0.001）方面有统计学显著改善。西妥昔单抗β联合FOLFIRI表现出可管理的毒性，且无新的安全信号。本研究表明，西妥昔单抗β联合FOLFIRI作为RAS/BRAF野生型mCRC患者的一线治疗提供了显著的临床益处。与单纯FOLFIRI相比，西妥昔单抗β联合FOLFIRI治疗导致中位PFS和OS延长，同时保持可管理的安全性，为该患者群体提供了一种新的治疗选择。
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