背景:索拉非尼目前是有症状的纤维瘤病(DTF)患者的推荐治疗方法之一。在这项研究中,我们旨在评估索拉非尼在DTF患者中的临床疗效和耐受性.
方法:年龄>18岁、组织学诊断为DTF且已接受索拉非尼治疗的患者被纳入这项前瞻性观察性研究。人口统计数据,临床资料,索拉非尼的初始剂量,治疗相关毒性,剂量修改,并记录反应。主要目标是评估客观反应率(ORR)。次要目标是评估无进展生存期(PFS),耐受性,和索拉非尼的不良反应。反应评估基于实体瘤1.1标准的反应评估标准。根据美国国家癌症研究所不良事件通用术语标准5.0版标准对不良反应进行分级。通过Kaplan-Meier分析计算事件发生时间,采用对数秩检验比较生存率。单变量和多变量cox回归分析用于寻找复发的独立预测因子。
结果:共有104名患者被纳入研究。研究人群的平均年龄为32岁(范围,18-81)年,66.35%的患者为女性。关于回应评估,ORR为46.1%,31.7%的患者病情稳定。阑尾部位的ORR(51.7%)高于腹部部位(27.2%)。1年和2年的PFS分别为86.6%(79.6-92.7%)和73.7%(62.4-82.8%),分别。三分之二(66.6%)的患者已经接受了某种形式的治疗。在分析的时候,70例(67.3%)患者继续索拉非尼。只有4.8%的人因进展而停止索拉非尼,10.5%由于不能容忍的不良反应,和17.3%由于其他原因。常见的治疗相关毒性为手足皮肤反应(HFSR)(89.4%),疲劳(79.8%),脱发(70.1%),和腹泻(48.0%)。在起始剂量≥400mg的患者中(48.0%的患者),12%的患者需要停药,58%需要进一步减少剂量,而在起始剂量为200mg时,只有约13%的患者需要减少剂量或停药(51.9%的患者)。由于较低的起始剂量,反应没有受到影响。
结论:索拉非尼在DTF中具有良好的活性,但它与显著的毒性有关。在HFSR和脱发较高的印度患者中,不良反应特征明显。由于起始剂量为400mg的剂量减少/停药率很高,印度患者的起始剂量为200mg.
Sorafenib is currently one of the recommended treatments for symptomatic patients with desmoid-type fibromatosis (DTF). In this study, we aim to assess the clinical efficacy and tolerability of sorafenib in DTF patients.
Patients aged>18 years with a histological diagnosis of DTF and who have received sorafenib were enroled in this prospective observational study. Demographic data, clinical profile, the initial dose of sorafenib, treatment-related toxicities, dose modifications, and responses were recorded. The primary objective was to assess the objective response rate (ORR). The secondary objectives were to evaluate progression-free survival (PFS), tolerability, and adverse effects of sorafenib. Response assessment was based on response evaluation criteria in solid tumours 1.1 criteria. Adverse effects were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 criteria. Time to event was calculated by Kaplan-Meier analysis, and survival was compared by log-rank test. Univariate and multivariable cox regression analysis were used to find independent predictors of relapse.
A total of 104 patients were enroled in the study. The median age of the study population was 32 (range, 18-81) years, and 66.35% of patients were females. On response assessment, ORR was 46.1% and stable disease was observed in 31.7% patients. ORR was higher in the appendicular site (51.7%) compared to the abdominal site (27.2%). PFS at 1 and 2 years was 86.6% (79.6-92.7%) and 73.7% (62.4-82.8%), respectively. Two-thirds (66.6%) of patients had already received some form of treatment. At the time of analysis, 70 (67.3%) patients were continuing sorafenib. Only 4.8% stopped sorafenib due to progression, 10.5% due to intolerable adverse effects, and 17.3% due to other reasons. The common treatment-related toxicities were hand-foot skin reaction (HFSR) (89.4%), fatigue (79.8%), alopecia (70.1%), and diarrhoea (48.0%). In the patients with a starting dose of ≥400 mg (48.0% of patients), discontinuation was necessitated in 12% of patients, and further dose reduction was required in 58%, while only about 13% required dose reduction or discontinuation at a starting dose of 200 mg (51.9% of patients). Responses were not compromised due to lower starting doses.
Sorafenib has good activity in DTF, but it is associated with significant toxicity. The adverse effect profile is distinct in Indian patients with higher HFSR and alopecia. Due to the high rate of dose reduction/discontinuation with a starting dose of 400 mg, a starting dose of 200 mg may be recommended in Indian patients.