FRESCO试验中按肝转移情况进行的亚组分析：比较呋喹替尼与安慰剂加最佳支持治疗用于中国转移性结直肠癌患者
Subgroup Analysis by Liver Metastasis in the FRESCO Trial Comparing Fruquintinib versus Placebo Plus Best Supportive Care in Chinese Patients with Metastatic Colorectal Cancer.
作者信息
Qin Shukui, Xu Rui-Hua, Shen Lin, Xu Jianming, Bai Yuxian, Yang Lei, Deng Yanhong, Chen Zhen-Dong, Zhong Haijun, Pan Hongming, Guo Weijian, Shu Yongqian, Yuan Ying, Zhou Jianfeng, Xu Nong, Liu Tianshu, Ma Dong, Wu Changping, Cheng Ying, Chen Donghui, Li Wei, Sun Sanyuan, Yu Zhuang, Cao Peiguo, Chen Haihui, Wang Jiejun, Wang Shubin, Wang Hongbing, Wang Ning, Zhang Bin, Zhang Qiang, Su Weiguo, Guo Xiaojun, Li Jin
机构信息
Cancer Center, Jinling Hospital, Nanjing, People's Republic of China.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China.
出版信息
Onco Targets Ther. 2021 Aug 11;14:4439-4450. doi: 10.2147/OTT.S307273. eCollection 2021.
OBJECTIVE
The aim of the present subgroup analysis of the FRESCO trial is to determine the efficacy and hepatotoxicity of fruquintinib in Chinese patients with metastatic CRC with liver metastasis (CRLM) who were receiving third-line or posterior-line therapy.
METHODS
Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Hazard ratio (HR) was estimated through Cox proportional hazards model. Hepatotoxicity was coded using the standardized MedDRA queries of hepatic failure, fibrosis, cirrhosis, and other liver injury-related conditions and graded using the Common Terminology Criteria Adverse Events grades. The efficacy of fruquintinib in patients with CRLM was evaluated in various subgroups.
RESULTS
A total of 287 (69.0%) patients with metastatic CRC had liver metastasis (LM, fruquintinib: 185 and placebo: 102). Median OS in patients with CRLM was significantly prolonged with fruquintinib compared with placebo (8.61 months vs 5.98 months; HR=0.59, 95% CI, 0.45-0.77, P<0.001). In patients with CRLM, the incremental median PFS for patients in the fruquintinib-treated group was significantly higher than in the placebo group (median PFS: 3.71 vs.1.84 months; HR=0.22, 95% CI: 0.17-0.30; P<0.001). Compared with placebo, significant improvements in OS were observed with fruquintinib in LM patients regardless of lung metastasis, prior target therapy, and K-RAS status. In patients with CRLM, treatment-emergent hepatotoxicities of any grade occurred in 7 (3.8%) patients in the fruquintinib group vs 2 (2.0%) in the placebo group.
CONCLUSION
Fruquintinib demonstrated a statistically significant increase in OS and PFS as compared with placebo in Chinese patients with CRLM. The hepatotoxicity of fruquintinib was less reported, and comparable with placebo in patients with CRLM.
CLINICALTRIALSGOV IDENTIFIER
NCT02314819.
目的
本FRESCO试验亚组分析的目的是确定呋喹替尼对接受三线或后线治疗的中国转移性结直肠癌伴肝转移（CRLM）患者的疗效和肝毒性。
方法
采用Kaplan-Meier法评估总生存期（OS）和无进展生存期（PFS）。通过Cox比例风险模型估计风险比（HR）。使用标准化的MedDRA查询对肝衰竭、纤维化、肝硬化和其他肝损伤相关疾病进行肝毒性编码，并使用《不良事件通用术语标准》分级。在各个亚组中评估呋喹替尼对CRLM患者的疗效。
结果
共有287例（69.0%）转移性结直肠癌患者发生肝转移（LM，呋喹替尼组：185例；安慰剂组：102例）。与安慰剂相比，呋喹替尼显著延长了CRLM患者的中位OS（8.61个月对5.98个月；HR=0.59，95%CI，0.45-0.77，P<0.001）。在CRLM患者中，呋喹替尼治疗组患者的中位PFS增量显著高于安慰剂组（中位PFS：3.71对1.84个月；HR=0.22，95%CI：0.17-0.30；P<0.001）。与安慰剂相比，无论是否有肺转移、既往靶向治疗和K-RAS状态，呋喹替尼在LM患者中均观察到OS有显著改善。在CRLM患者中，呋喹替尼组7例（3.8%）患者发生任何级别的治疗中出现的肝毒性，而安慰剂组为2例（2.0%）。
结论
与安慰剂相比，呋喹替尼在中国CRLM患者中显示出OS和PFS有统计学显著增加。呋喹替尼的肝毒性报告较少，在CRLM患者中与安慰剂相当。
临床试验注册号
NCT02314819。
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