West Cancer Center, Germantown, TN, USA.
Léon Bérard Centre and Claude Bernard University, Lyon, France.
Cancer Treat Rev. 2020 Jun;86:101993. doi: 10.1016/j.ctrv.2020.101993. Epub 2020 Feb 20.
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.
瑞戈非尼是一种口服酪氨酸激酶抑制剂（TKI），已获批准用于治疗难治性转移性结直肠癌（mCRC）、既往接受伊马替尼和舒尼替尼治疗的晚期胃肠道间质瘤（GIST），以及索拉非尼治疗进展后的不可切除肝细胞癌（HCC）。瑞戈非尼最初基于随机、安慰剂对照、III 期 CORRECT 试验中总生存期（OS）的改善而获得 mCRC 的批准，该试验在随机、安慰剂对照、III 期 CONCUR 试验中对亚洲患者进行了扩展人群验证。在 GIST 中的批准，以及最近在 HCC 中的批准，分别基于随机、安慰剂对照、III 期 GRID 和 RESORCE 试验的结果。在这篇综述中，我们全面总结了瑞戈非尼在 mCRC、GIST 和 HCC 获批的临床证据，介绍了瑞戈非尼在其他肿瘤类型（即胃食管癌、肉瘤、胆管癌和胶质母细胞瘤）中活性的新证据，并结合其作用机制讨论了正在进行的试验。我们描述了瑞戈非尼的最新进展和关键经验教训，包括使用剂量优化策略管理常见药物相关毒性的重要性、寻找预测治疗反应的生物标志物，以及强调了瑞戈非尼在不同肿瘤中的一些未解决的问题和未来方向。
