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Drugs. 2018 Jul;78(11):1133-1144. doi: 10.1007/s40265-018-0938-y.
Regorafenib (Stivarga) is an oral small-molecule multiple kinase inhibitor. It is indicated worldwide for patients with metastatic colorectal cancer (mCRC). In the EU and USA it is indicated for patients with mCRC who have been previously treated with, or are not considered candidates for available therapies, including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and, if RAS wild-type, an anti-EGFR therapy. In Japan, it is indicated for the treatment of unresectable, advanced/recurrent CRC. The addition of regorafenib to best supportive care prolonged median overall survival (OS; by up to 2.5 months) and progression-free survival (PFS; by up to 1.5 months) relative to the addition of placebo in double-blind phase 3 studies (CORRECT and CONCUR) in patients with mCRC who had progressed after failure of standard therapy. Health-related quality of life was not adversely affected with regorafenib relative to placebo. A large open-label phase 3 study (CONSIGN) and several large real-world studies supported the efficacy of regorafenib in this setting. Regorafenib had a generally manageable tolerability profile, which was consistent with the profile of a typical small-molecule multiple kinase inhibitor. Treatment-related adverse events (AEs), mostly of mild or moderate severity, were reported in the majority of patients receiving regorafenib, with dermatological toxicities and liver enzyme elevations among the most common AEs. Although identification of biomarkers/parameters predicting efficacy outcomes with regorafenib will help to individualize therapy, current evidence indicates that regorafenib is a valuable treatment option for patients with refractory mCRC who have a very poor prognosis.
瑞戈非尼(Stivarga)是一种口服小分子多激酶抑制剂。它在全球范围内被批准用于转移性结直肠癌(mCRC)患者。在欧盟和美国,它被批准用于先前接受过治疗或不适合现有治疗方法的 mCRC 患者,包括基于氟嘧啶的化疗、抗 VEGF 治疗,如果 RAS 野生型,还包括抗 EGFR 治疗。在日本,它被批准用于治疗不可切除的、晚期/复发性 CRC。与安慰剂相比,在 CORRECT 和 CONCUR 这两项针对 mCRC 患者的双盲 3 期研究中,瑞戈非尼联合最佳支持治疗可显著延长中位总生存期(OS;最多延长 2.5 个月)和无进展生存期(PFS;最多延长 1.5 个月),这些患者在标准治疗失败后病情进展。与安慰剂相比,瑞戈非尼对健康相关生活质量没有不利影响。一项大型开放标签 3 期研究(CONSIGN)和几项大型真实世界研究支持了瑞戈非尼在该治疗环境中的疗效。瑞戈非尼的耐受性通常较好,与典型的小分子多激酶抑制剂一致。大多数接受瑞戈非尼治疗的患者报告了治疗相关不良事件(AE),大多数为轻或中度严重程度,最常见的 AE 包括皮肤毒性和肝酶升高。尽管鉴定与瑞戈非尼疗效相关的生物标志物/参数将有助于个体化治疗,但目前的证据表明,瑞戈非尼是一种非常适合预后极差的难治性 mCRC 患者的治疗选择。