Purpose

Despite advances in the treatment of colorectal cancer, third-line treatment options are still limited. Regorafenib was approved in 2012 for the treatment of patients with metastatic colorectal cancer previously treated with approved standard therapy. The purpose of this review is to present existing clinical data on regorafenib.

Method

We systematically searched the PubMed and Embase databases, as well as ASCO and ESMO conference abstracts, for studies in English including ≥30 patients, evaluating the efficacy and safety of regorafenib in patients with metastatic colorectal cancer. A meta-analysis was conducted on the published, randomized phase III trials.

Results

24 eligible studies were included. In two phase III trials, regorafenib significantly increased overall survival (OS), progression free survival (PFS), and disease control rate when compared to placebo. Survival benefits of 1.4 and 2.5 months were presented. The meta-analysis indicated a significant greater treatment effect on OS (hazard ratio 0.67) and PFS (hazard ratio 0.40), compared to placebo. The non-randomized studies mostly supported these results.

The most frequently reported adverse events were hand-foot-skin reaction (25%–86%), hypertension (11%–47%) and fatigue (2%–73%).

Conclusion

Large phase III randomized trials indicate that regorafenib provides a benefit in OS and PFS when compared to placebo. Adverse events were common, but manageable and typical of multi-target tyrosine kinase inhibitors. Further research is needed to investigate alternative approaches to the dosing of regorafenib and to explore clinical and molecular biomarkers that can guide patient selection.

中文翻译：

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瑞格非尼治疗转移性结直肠癌的疗效和安全性：系统评价

目的

尽管在结直肠癌的治疗方面取得了进步，但三线治疗的选择仍然有限。Regorafenib于2012年获准用于治疗转移性结直肠癌患者，此前该患者已接受批准的标准疗法治疗。这篇综述的目的是介绍雷戈非尼的现有临床数据。

方法

我们系统地搜索了PubMed和Embase数据库以及ASCO和ESMO会议摘要，以英语进行研究（包括30例以上患者），评估了雷戈非尼在转移性结直肠癌患者中的疗效和安全性。对已发表的随机III期临床试验进行荟萃分析。

结果

纳入24项合格研究。在两项III期试验中，与安慰剂相比，雷戈非尼显着提高了总生存期（OS），无进展生存期（PFS）和疾病控制率。提出了1.4和2.5个月的生存获益。荟萃分析表明，与安慰剂相比，对OS（危险比0.67）和PFS（危险比0.40）的治疗效果显着增强。非随机研究大多支持这些结果。

最常见的不良反应是手足皮肤反应（25％–86％），高血压（11％–47％）和疲劳（2％–73％）。

结论

大型的III期随机试验表明，与安慰剂相比，雷戈非尼在OS和PFS方面具有益处。不良事件是常见的，但可控且是多靶酪氨酸激酶抑制剂的典型事件。需要进一步的研究来研究瑞戈非尼给药的替代方法，并探索可指导患者选择的临床和分子生物标志物。