Objective: To evaluate the dose, efficacy and tolerability of regorafenib in a real-world clinical setting of metastatic colorectal cancer patients. Methods: The clinical data of patients with metastatic colorectal cancer who had received at least two previous treatment lines treated with regorafenib from May 2018 to December 2019 at National Cancer Center/Cancer Hospital was retrospectively analyzed. Patients'demographics, treatment, dosimetry, safety and survival data were collected. The primary endpoint was overall survival (OS). Results: A total of 114 patients were enrolled in this study, including male 83 and female 31, with a median age of 61.Of all patients, 83 were treated with regorafenib and 31 were given combination therapy with regorafenib. Starting dose was 80 mg in 57 (50.0%) patients, 120 mg in 24 (21.1%) patients, and 160 mg in 28 (24.6%) patients. Dose increases were observed in 30.9% (25/81) of patients receiving 80 mg and 120 mg as the initial dose. Forty-five (39.5%) and 36 (31.6%) patients took the last daily dose of 80 mg and 120 mg, respectively. Median follow-up time was 8.5 months.Objective response rate (ORR) and disease control rate(DCR) were 1.0% and 52.1%, respectively. The median progression free survivalrate (PFS) was 2.4 moths (95%CI: 0.80-10.57), median OS was 11.0 moths(95%CI: 9.03-not available). The difference of the PFS and OS in the different dose groups was not statistically significant. But patients who received 120 mg regorafenib showed much longer survival with a median OS of 16.7 month. The difference of survival between the regorafenib group and combination group was not statistically significant either. Twenty patients continued with regorafenib as treatment even after progression. These patients had longer survival compared with those (n=52) who stopped regorafenib with median OS of 16.7 month vs 9.1 month (χ(2)=2.305, P=0.116), respectively.There were 7.9%(9/114) of the patients who discontinued regorafenib therapy because of the adverse event, such as hand-foot skin reaction (HFSR), gastrointestinal bleeding, proteinuria and liver function injury. Conclusions: Patients with advanced colorectal cancer who failed to respond to standard therapy have a good survival benefit. The initial dose of 120 mg of regorafenib has a better risk/benefit ratio and is more suitable for patients with advanced colorectal cancer.
目的： 分析瑞戈非尼在晚期结直肠癌真实世界中的应用剂量、疗效及安全性。 方法： 收集2018年5月至2019年12月在中国医学科学院肿瘤医院接受瑞戈非尼治疗的经标准方案治疗失败的晚期结直肠癌患者的临床资料，分析瑞戈非尼的剂量特点、疗效及安全性。主要终点指标为总生存期（OS）。 结果： 共114例患者纳入本研究，其中男83例，女31例；中位年龄61岁。瑞戈非尼单药治疗83例，联合治疗31例。起始剂量80、120、160 mg分别为57例（50.0%）、24例（21.1%）和28例（24.6%）。30.9%（25/81）的低起始剂量患者在治疗过程中进行了剂量上调。最终日剂量80和120 mg分别为45例（39.5%）和36例（31.6%）。中位随访时间8.5个月，客观缓解率（ORR）1.0%，疾病控制率（DCR）52.1%，中位无进展生存期（PFS）2.4个月（95%CI：0.80~10.57），OS 11.0个月（95%CI：9.03~缺失值）。不同最终日剂量间的PFS及OS差异无统计学意义（P>0.05），120 mg组中位OS最长，达16.7个月。单药和联合治疗的中位OS差异无统计学意义（P>0.05）。疾病进展后继续瑞戈非尼治疗患者（20例）的中位OS长于停用者（52例），分别为16.7和9.1个月（χ(2)=2.305，P=0.116）。7.9%（9/114）的患者因不良事件停药，包括手足皮肤反应、消化道出血、蛋白尿、肝功能损伤。 结论： 瑞戈非尼治疗经标准方案治疗失败的晚期结直肠癌患者的生存获益良好。起始剂量120 mg的瑞戈非尼具有较好的风险/获益比，较为适合晚期结直肠癌患者。.
Keywords: Colorectal neoplasms; Efficacy; Real world; Regorafenib.