Clinical Oncology Unit, Careggi University Hospital, 50134 Florence, Italy.
Department of Health Science, University of Florence, 50139 Florence, Italy.
Int J Mol Sci. 2023 Mar 19;24(6):5840. doi: 10.3390/ijms24065840.
The management of patients with metastatic colorectal cancer (mCRC) has the continuum of care as the treatment paradigm. To date, trifluridine/tipiracil, a biochemically modulated fluoropyrimidine, and regorafenib, a multi-kinase inhibitor, remain the main options for the majority of patients who progressed to standard doublet- or triplet-based chemotherapies, although a tailored approach could be indicated in certain circumstances. Being highly selective for vascular endothelial growth factor receptor (VEGFR)-1, -2 and -3, fruquintinib demonstrated a strong anti-tumor activity in preclinical models and received approval from China's National Medical Products Administration (NMPA) in 2018 for the treatment of patients with chemo-refractory mCRC. The approval was based on the results of the phase III FRESCO trial. Then, in order to overcome geographic differences in clinical practice, the FRESCO-2 trial was conducted in the US, Europe, Japan, and Australia. In a heavily pretreated patient population, the study met its primary endpoint, demonstrating an advantage of fruquintinib over a placebo in overall survival (OS). Here, we review the clinical development of fruquintinib and its perspectives in gastrointestinal cancers. Then, we discuss the introduction of fruquintinib in the continuum of care of CRC paying special attention to unmet needs, including the identification of cross-resistant and potentially susceptible populations, evaluation of radiological response, and identification of novel biomarkers of clinical benefit.
转移性结直肠癌（mCRC）患者的管理以连续护理为治疗模式。迄今为止，三氟尿苷/替匹嘧啶，一种生化调节的氟嘧啶，和瑞戈非尼，一种多激酶抑制剂，仍然是大多数进展为标准二联或三联化疗的患者的主要选择，尽管在某些情况下可能需要个体化治疗。高度选择性的血管内皮生长因子受体（VEGFR）-1、-2 和 -3，呋喹替尼在临床前模型中表现出强烈的抗肿瘤活性，并于 2018 年获得中国国家药品监督管理局（NMPA）批准，用于治疗化疗耐药的 mCRC 患者。该批准基于 III 期 FRESCO 试验的结果。然后，为了克服临床实践中的地理差异，在美国、欧洲、日本和澳大利亚进行了 FRESCO-2 试验。在预处理过的患者人群中，该研究达到了主要终点，证明了呋喹替尼在总生存期（OS）方面优于安慰剂。在这里，我们回顾了呋喹替尼的临床开发及其在胃肠道癌症中的前景。然后，我们讨论了呋喹替尼在 CRC 连续护理中的引入，特别关注未满足的需求，包括识别交叉耐药和潜在敏感人群、评估影像学反应和识别新的临床获益生物标志物。
