Head and Neck Cancer Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Medical Oncology Department, University of Milan, Milan, Italy.
Endocrine. 2021 Sep;73(3):641-647. doi: 10.1007/s12020-021-02702-4. Epub 2021 Apr 2.
Radioactive-iodine (RAI)-resistant differentiated thyroid cancer (DTC) patients benefit from multi-kinase inhibitors (MKIs), such as lenvatinib. Incidence of treatment-related (TR) late toxicities has been not yet described.
From January 2015 to June 2019 we retrospectively reviewed clinical records of patients with RAI-resistant DTC treated with lenvatinib at Istituto Nazionale dei Tumori (Milan, Italy). New side effect of any grade, appeared after 12 months of lenvatinib, was defined as late adverse event (AE). Descriptive analyses were performed. Survival curves were estimated with Kaplan-Meier method and compared with log-rank test.
Thirty-seven patients were included, 65% had ≥65 years and 68% were female. Thirty patients received lenvatinib for >12 months. Lenvatinib was started at ≤20 mg/daily in 59% of patients, 64% were ≥65 years. The frequency of late AEs was 80% and cardiovascular toxicity was the most common (57%). There was no difference in the incidence of late AEs between younger/older population (77% and 82%, respectively). Median lenvatinib treatment duration (TD) was 39.96 months (95% CI 21.64-NR): 39.96 months for patients <65 years (95% CI: 13.25-NR) and 37.53 months for those ≥65 years, respectively (95% CI: 15.85-NR). Median overall survival (OS) was 39.96 months (95% CI: 21.84-NR), no statistically differences in OS was observed between younger (<65 years) and older patients (≥65 years) (HR 1.013; 95% CI 0.963-1.065; p = 0.62).
Late toxicity burden of lenvatinib is not negligible. Cardiovascular toxicity remains the principal side effect even after a prolonged lenvatinib exposition.
放射性碘（RAI）耐药分化型甲状腺癌（DTC）患者受益于多激酶抑制剂（MKIs），如仑伐替尼。尚未描述治疗相关（TR）晚期毒性的发生率。
本研究回顾性分析了 2015 年 1 月至 2019 年 6 月期间在意大利国家肿瘤研究所（米兰）接受仑伐替尼治疗的 RAI 耐药 DTC 患者的临床记录。任何等级的新的治疗相关副作用，在仑伐替尼治疗 12 个月后出现，被定义为晚期不良事件（AE）。进行描述性分析。采用 Kaplan-Meier 法估计生存曲线，并采用对数秩检验比较。
共纳入 37 例患者，65%患者年龄≥65 岁，68%为女性。30 例患者接受仑伐替尼治疗时间超过 12 个月。59%的患者仑伐替尼起始剂量≤20mg/d，64%的患者年龄≥65 岁。晚期 AE 的发生率为 80%，心血管毒性最常见（57%）。年轻/老年患者晚期 AE 的发生率无差异（分别为 77%和 82%）。仑伐替尼治疗的中位时间（TD）为 39.96 个月（95%CI：21.64-NR）：年龄<65 岁的患者中位 TD 为 39.96 个月（95%CI：21.84-NR），年龄≥65 岁的患者中位 TD 为 37.53 个月（95%CI：15.85-NR）。中位总生存期（OS）为 39.96 个月（95%CI：21.84-NR），年龄<65 岁（<65 岁）和年龄≥65 岁的患者（≥65 岁）之间 OS 无统计学差异（HR 1.013；95%CI 0.963-1.065；p=0.62）。
仑伐替尼的晚期毒性负担不容忽视。即使仑伐替尼暴露时间延长，心血管毒性仍然是主要的副作用。
