Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan.
Oncologist. 2019 Jul;24(7):e450-e457. doi: 10.1634/theoncologist.2018-0377. Epub 2019 Jan 3.
Regorafenib improved the overall survival (OS) of patients with metastatic colorectal cancer (mCRC) who progress after standard therapies in two phase III trials. The present large-scale prospective observational study evaluated the safety and effectiveness of regorafenib administered to Japanese patients with mCRC in real-life setting.
Patients with mCRC were prospectively registered and initially received ≤160 mg oral regorafenib daily, at the investigator's discretion, for weeks 1-3 of each 4-week cycle. The study's primary aim was to assess safety, particularly unexpected clinically significant adverse drug reactions (ADRs). A Cox's proportional hazards model was used to evaluate the association between OS, hand-foot skin reaction (HFSR), and baseline characteristics.
We evaluated 1,227 of 1,301 patients (enrolled from March 2013 to May 2015). ADRs occurred in 89.3% of patients (mostly within the first 4 weeks) and were a major reason for discontinuing treatment. The most frequent ADRs were HFSR, liver injury, and hypertension. The cumulative incidence of HFSR and liver injury was higher in patients who initially received 160 mg than in those who received ≤120 mg. The incidence of hypertension and fatigue was similar between groups. Median OS was 6.9 months (95% confidential interval, 6.4-7.4). OS was associated with early onset of HFSR and good performance status (PS) but not with the initial dose.
The outcomes of this study were consistent with those of clinical trials. There were no new safety concerns. Regorafenib treatment would not be recommended for patients with higher PS.
Previous clinical trials demonstrated regorafenib improved overall survival in patients with metastatic colorectal cancer who progress after standard chemotherapies. Because the eligibility criteria of the trials were restricted compared with a real-world setting, the data from the trials may not fully represent the profiles of regorafenib in clinical practice. This large-scale observational study showed that the safety and effectiveness of regorafenib in clinical practice were generally consistent with previous trials. The majority of patients reported adverse drug reactions within the first 4 weeks, most commonly hand-foot skin reaction. Regorafenib treatment would not be recommended for patients with higher performance status.
regorafenib 在两项 III 期试验中改善了标准治疗后进展的转移性结直肠癌（mCRC）患者的总生存期（OS）。本大规模前瞻性观察性研究评估了regorafenib 在日本 mCRC 患者中的安全性和有效性。
前瞻性注册患者，mCRC 患者最初在每个 4 周周期的第 1-3 周，根据研究者的判断，每天接受≤160mg 口服regorafenib。该研究的主要目的是评估安全性，特别是意外的具有临床意义的药物不良反应（ADR）。采用 Cox 比例风险模型评估 OS、手足皮肤反应（HFSR）与基线特征之间的关联。
我们评估了 1227 例患者中的 1301 例（2013 年 3 月至 2015 年 5 月入组）。89.3%的患者发生 ADR（主要发生在最初的 4 周内），是停药的主要原因。最常见的 ADR 是 HFSR、肝损伤和高血压。初始接受 160mg 的患者 HFSR 和肝损伤的累积发生率高于接受≤120mg 的患者。两组间高血压和疲劳的发生率相似。中位 OS 为 6.9 个月（95%置信区间，6.4-7.4）。OS 与 HFSR 的早期发作和良好的表现状态（PS）有关，但与初始剂量无关。
该研究的结果与临床试验一致。没有新的安全性问题。不建议 PS 较高的患者使用 regorafenib。
先前的临床试验表明，regorafenib 改善了标准化疗后进展的转移性结直肠癌患者的总生存期。由于试验的入选标准与真实世界环境相比受到限制，因此试验数据可能无法充分反映 regorafenib 在临床实践中的情况。本大规模观察性研究表明，regorafenib 在临床实践中的安全性和有效性与先前的试验基本一致。大多数患者在最初的 4 周内报告了不良反应，最常见的是手足皮肤反应。不建议 PS 较高的患者使用 regorafenib。
