Gotfrit J, Vickers M, Sud S, Asmis T, Cripps C, Goel R, Hsu T, Jonker D, Goodwin R
The Ottawa Hospital Research Institute and.
Division of Medical Oncology, Department of Medicine, University of Ottawa, Ottawa, ON.
Curr Oncol. 2017 Aug;24(4):234-239. doi: 10.3747/co.24.3562. Epub 2017 Aug 31.
Various tyrosine kinase signalling pathways affect the development and progression of colorectal cancer (crc). In clinical trials, regorafenib has been associated with a survival benefit in metastatic crc (mcrc). We assessed the safety and efficacy of regorafenib in real-world patients.
In a retrospective review of patients with mcrc treated with regorafenib at our institution from 2013 to 2015, patient demographics, treatment, and survival data were collected. Progression-free survival (pfs) and overall survival (os) were estimated using the Kaplan-Meier method.
In total, 48 patients were offered regorafenib, and 35 (73%) started treatment. Of the patients who started regorafenib, 57% were men. Median age in the cohort was 61 years, and all patients had a performance status in the range 0-2. Time from diagnosis of mcrc to regorafenib treatment was more than 18 months in 71% of patients. Starting dose was 160 mg in 54% of the patients, 120 mg in 40%, and 80 mg in 6%. Dose reductions occurred in 34% of the patients, and interruptions, in 29%. Best response was progressive disease (60%) and stable disease (17%); response in the rest of the patients was unknown. The most common adverse events on regorafenib (any grade) were fatigue (57%), hyperbilirubinemia (43%), thrombocytopenia (37%), anorexia (31%), and hypertension (31%). The most common grade 3 or 4 adverse events were fatigue (29%), hypophosphatemia (17%), weight loss (11%), and hyperbilirubinemia (9%). Common reasons for discontinuing regorafenib included progressive disease (51%) and toxicity (26%). In patients treated with regorafenib, pfs was 2.4 months (95% confidence interval: 1.8 to 3.3 months) and os was 5.6 months (95% confidence interval: 3.7 to 8.9 months). No factors were associated with survival in univariate or multivariate analysis.
In a real-world setting, regorafenib is associated with survival similar to that reported in the randomized controlled trials, but at the expense of toxicity leading to discontinuation in many patients. Future studies of regorafenib should focus on identifying the patients most likely to benefit and on minimizing toxicity.
多种酪氨酸激酶信号通路影响结直肠癌（CRC）的发生和发展。在临床试验中，瑞戈非尼已被证明可使转移性结直肠癌（mCRC）患者受益。我们评估了瑞戈非尼在真实世界患者中的安全性和疗效。
回顾性分析2013年至2015年在我院接受瑞戈非尼治疗的mCRC患者，收集患者的人口统计学、治疗及生存数据。采用Kaplan-Meier法评估无进展生存期（PFS）和总生存期（OS）。
共有48例患者接受瑞戈非尼治疗，35例（73%）开始治疗。开始接受瑞戈非尼治疗的患者中，57%为男性。队列患者的中位年龄为61岁，所有患者的体能状态评分为0 - 2分。71%的患者从mCRC诊断到接受瑞戈非尼治疗的时间超过18个月。54%的患者起始剂量为160 mg，40%为120 mg，6%为80 mg。34%的患者出现剂量减少，29%的患者出现治疗中断。最佳疗效为疾病进展（60%）和疾病稳定（17%）；其余患者的疗效未知。瑞戈非尼治疗期间最常见的任何级别的不良事件为疲劳（57%）、高胆红素血症（43%）、血小板减少（37%）、厌食（31%）和高血压（31%）。最常见的3级或4级不良事件为疲劳（29%）、低磷血症（17%）、体重减轻（11%）和高胆红素血症（9%）。停用瑞戈非尼的常见原因包括疾病进展（51%）和毒性反应（26%）。接受瑞戈非尼治疗的患者，PFS为2.4个月（95%置信区间：1.8至3.3个月），OS为5.6个月（95%置信区间：3.7至8.9个月）。单因素和多因素分析均未发现与生存相关的因素。
在真实世界中，瑞戈非尼的生存获益与随机对照试验报道的相似，但代价是毒性反应导致许多患者停药。未来瑞戈非尼的研究应聚焦于识别最可能受益的患者并尽量减少毒性反应。
