Dasari Arvind, Eng Cathy, Lonardi Sara, Garcia-Carbonero Rocio, Masuishi Toshiki, Cremolini Chiara, Ghiringhelli François, Hubbard Joleen, Bekaii-Saab Tanios, Jones Jeremy, Xu Rui-Hua, Shen Lin, Xu Jianming, Bai Yuxian, Deng Yanhong, Yuan Ying, Wei Wei, Lin Jianchang, Chen Lucy, Yang Zhao, Schelman William R, Qin Shukui, Li Jin
Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Medicine, Division of Hematology and Oncology, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Eur J Cancer. 2025 Sep 9;227:115641. doi: 10.1016/j.ejca.2025.115641. Epub 2025 Jul 13.
In the phase 3 FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) studies, fruquintinib vs placebo, plus best supportive care, significantly improved overall survival (OS) in patients with metastatic colorectal cancer (mCRC). These studies were conducted in temporally and geographically diverse populations that received distinct prior therapies; FRESCO patients were less pretreated than FRESCO-2 patients. This analysis assessed the efficacy and safety of fruquintinib in a less pretreated global population than the FRESCO-2 intention-to-treat (ITT) population.
In FRESCO and FRESCO-2, patients were randomized 2:1 to receive oral fruquintinib 5 mg or matched placebo. Profile matching was undertaken using the following variables: age, Eastern Cooperative Oncology Group performance status, RAS status, number of metastatic sites, liver metastases, and number of prior treatment lines. OS, progression-free survival (PFS), and safety were assessed.
Of 691 patients in FRESCO-2, 152 (fruquintinib n = 103; placebo n = 49) were matched to the FRESCO ITT population. After matching, the FRESCO-2 subset and FRESCO ITT population had similar baseline characteristics and pretreatment profiles. In the FRESCO-2 subset, FRESCO ITT population, and combined dataset, respectively, unstratified hazard ratios for OS were 0.63, 0.62, and 0.63, and for PFS were 0.34, 0.27, and 0.30; 63.7 %, 61.2 %, and 61.8 % of patients had grade ≥ 3 treatment-emergent adverse events with fruquintinib.
Clinically meaningful efficacy of fruquintinib was maintained in a global patient population with less pretreated mCRC than the FRESCO-2 ITT population, with no new safety signals, demonstrating efficacy regardless of prior treatment lines.
在3期FRESCO（NCT02314819）和FRESCO-2（NCT04322539）研究中，呋喹替尼与安慰剂加最佳支持治疗相比，显著改善了转移性结直肠癌（mCRC）患者的总生存期（OS）。这些研究在时间和地域上不同的人群中进行，这些人群接受了不同的既往治疗；FRESCO研究中的患者预处理程度低于FRESCO-2研究中的患者。本分析评估了呋喹替尼在一个预处理程度低于FRESCO-2意向性治疗（ITT）人群的全球人群中的疗效和安全性。
在FRESCO和FRESCO-2研究中，患者按2:1随机分组，接受口服呋喹替尼5mg或匹配的安慰剂。使用以下变量进行轮廓匹配：年龄、东部肿瘤协作组体能状态、RAS状态、转移部位数量、肝转移情况和既往治疗线数。评估总生存期（OS）、无进展生存期（PFS）和安全性。
在FRESCO-2研究的691例患者中，152例（呋喹替尼组n = 103；安慰剂组n = 49）与FRESCO ITT人群匹配。匹配后，FRESCO-2亚组和FRESCO ITT人群具有相似的基线特征和预处理情况。在FRESCO-2亚组、FRESCO ITT人群和合并数据集中，OS的未分层风险比分别为0.63、0.62和0.63，PFS的未分层风险比分别为0.34、0.27和0.30；接受呋喹替尼治疗的患者中，分别有63.7%、61.2%和61.8%发生了≥3级治疗中出现得不良事件。
在一个预处理程度低于FRESCO-2 ITT人群的全球mCRC患者人群中，呋喹替尼维持了具有临床意义的疗效，且无新的安全信号，表明无论既往治疗线数如何，其均有效。
