Regorafenib is an oral tyrosine kinase inhibitor (TKI) approved for the treatment of refractory metastatic colorectal cancer (mCRC), advanced gastrointestinal stromal tumors (GIST) previously treated with imatinib and sunitinib, and unresectable hepatocellular carcinoma (HCC) following progression on sorafenib. Regorafenib was initially approved for mCRC based on improved overall survival (OS) in the randomized, placebo-controlled, phase 3 CORRECT trial, which was confirmed in an expanded population of Asian patients in the randomized, placebo-controlled phase 3 CONCUR trial. Approvals in GIST, and more recently in HCC, were based on the results from the randomized, placebo-controlled, phase 3 GRID and RESORCE trials, respectively. In this review, we provide a comprehensive summary of the clinical evidence for approval of regorafenib in mCRC, GIST, and HCC, present emerging evidence of regorafenib activity in other tumor types (namely, gastroesophageal cancer, sarcomas, biliary tract cancer, and glioblastoma), and discuss trials in progress within the context of regorafenib's mechanism of action. We describe recent advances and key lessons learned with regorafenib, including the importance of managing common drug-related toxicities using dose-optimization strategies, the search for biomarkers to predict response to treatment, and highlight some of the unaddressed questions and future directions for regorafenib across tumors.

中文翻译：

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瑞格非尼在治疗晚期癌症中的作用不断发展。

Regorafenib是一种口服酪氨酸激酶抑制剂（TKI），已被批准用于治疗难治性转移性结直肠癌（mCRC），先前接受过伊马替尼和舒尼替尼治疗的晚期胃肠道间质瘤（GIST），以及索拉非尼治疗后发生的不可切除的肝细胞癌（HCC）。瑞戈非尼最初是根据改善的总生存期（OS）在随机，安慰剂对照的3期CORRECT试验中批准用于mCRC的，该研究在随机，安慰剂对照的3期CONCUR试验中得到了更多亚洲患者的证实。GIST和最近在HCC中的批准分别基于随机，安慰剂对照，3期GRID和RESORCE试验的结果。在这篇综述中，我们提供了瑞格非尼在mCRC，GIST，HCC和HCC提出了瑞戈非尼在其他肿瘤类型（即胃食管癌，肉瘤，胆道癌和胶质母细胞瘤）中活性的新兴证据，并讨论了瑞戈非尼作用机制下正在进行的试验。我们描述了雷戈非尼的最新进展和主要经验教训，包括使用剂量优化策略管理常见药物相关毒性的重要性，寻找生物标记物以预测对治疗的反应，并重点介绍了雷戈非尼的一些未解决的问题和未来发展方向肿瘤。