BACKGROUND Regorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regorafenib for patients with mCRC in real-world clinical practice. METHODS The international, prospective, CORRELATE study recruited patients with mCRC previously treated with approved therapies, for whom the decision to treat with regorafenib was made by the treating physician according to the local health authority approved label. The primary objective was safety, assessed by treatment-emergent adverse events (TEAEs; National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03). RESULTS A total of 1037 patients were treated. The median age was 65 years (range: 24-93); 87% of patients had Eastern Cooperative Oncology Group performance status 0-1, 56% of patients had KRAS, 7% had NRAS and 4% had BRAF mutations. The initial regorafenib dose was 160 mg/day in 57% of patients. The most common grade III or IV drug-related TEAEs were fatigue (9%), hand-foot skin reaction (7%) and hypertension (6%). Drug-related grade V (fatal) TEAEs occurred in 1% of patients. Dose reductions for drug-related TEAEs occurred in 24% of patients. Median OS was 7.7 months (95% confidence interval [CI]: 7.2-8.3), and median progression-free survival (PFS) was 2.9 months (95% CI: 2.8-3.0). CONCLUSIONS In this real-world, observational study of patients with mCRC, the regorafenib toxicity profile was similar to that reported in phase III trials. The starting dose for almost half of patients was less than the approved 160-mg dose, and the median OS and PFS were in the range observed in phase III trials. TRIAL REGISTRATION NCT02042144.

中文翻译：

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在前瞻性，观察性CORRELATE研究中，regorafenib在转移性结直肠癌患者中的安全性和有效性在常规临床实践中。

背景在第三期试验中，瑞戈非尼与难治性转移性结直肠癌（mCRC）患者相比，总生存期（OS）与安慰剂相比延长。我们在现实世界的临床实践中对雷戈非尼治疗mCRC患者进行了观察性研究。方法该国际前瞻性CORRELATE研究招募了先前接受过批准疗法治疗的mCRC患者，由主治医师根据当地卫生当局批准的标签决定使用regorafenib进行治疗。主要目标是安全性，通过紧急治疗不良事件进行评估（TEAE；美国国家癌症研究所不良事件通用术语标准，版本4.03）。结果共治疗了1037例患者。中位年龄为65岁（范围：24-93）；87％的患者患有东部合作肿瘤小组的工作状态为0-1，56％的患者患有KRAS，7％的患者患有NRAS，4％的患者患有BRAF突变。在57％的患者中，瑞戈非尼的初始剂量为160毫克/天。最常见的与III或IV级药物相关的TEAE是疲劳（9％），手足皮肤反应（7％）和高血压（6％）。1％的患者发生了药物相关的V级（致命）TEAE。与药物相关的TEAE的剂量减少发生在24％的患者中。OS中位数为7.7个月（95％置信区间[CI]：7.2-8.3），中位无进展生存期（PFS）为2.9个月（95％CI：2.8-3.0）。结论在这项针对mCRC患者的真实观察研究中，雷戈非尼的毒性特征与III期临床试验中报道的相似。几乎一半患者的起始剂量小于批准的160毫克剂量，OS和PFS的中位数在III期试验中观察到的范围内。试用注册NCT02042144。