Colombo Elena, Ducceschi Monika, Cavalieri Stefano, Polignano Maggie, Bini Marta, Ambrosini Paolo, De Monte Matteo, Montelatici Giulia, Russo Alessandra, Bellia Valentina, Bhoori Sharrie, Bergamini Cristiana, Alfieri Salvatore, Nuzzolese Imperia, Ottini Arianna, Mazzaferro Vincenzo, Raspagliesi Francesco, Licitra Lisa, Mantiero Mara
Head and Neck Medical Oncology Department, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
Gynecologic Oncology Department, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy.
Ther Adv Med Oncol. 2025 Sep 12;17:17588359251359905. doi: 10.1177/17588359251359905. eCollection 2025.
Lenvatinib (LEN) is a multikinase inhibitor used for different tumors: advanced differentiated thyroid cancers progressed or resistant to radioiodine (RAIR DTC), adenoid cystic carcinoma of salivary glands (AdCC), hepatocellular carcinoma (HCC), and endometrial carcinoma (EC). In the real-world setting, patients eligible for LEN often have multiple comorbidities and/or impaired Eastern Cooperative Oncology Group performance status (ECOG PS). In HCC, patients with body weight (BW) < 60 kg require a low starting dose of LEN; in thyroid cancers (TC), BW has a clinically relevant effect on steady-state exposure to LEN. It is currently unknown whether BW can vary during LEN treatment across different histologies.
This study aims to investigate toxicities, duration of treatment (DoT), and to describe BW and body mass index (BMI) intrapatient variations in the real-world setting.
Retrospective observational study conducted in a tertiary cancer center.
We collected clinical features and AEs from consecutive adult patients who started LEN for DTC, AdCC, HCC, or EC from January 2015 to April 2023. LEN first and last doses were estimated as a percentage of the standard dose approved for each indication. Differences in the BMI distribution assessed at baseline and end of treatment were assessed with Mann-Whitney test. Differences in intrapatient BMI variation were assessed with Kruskal-Wallis test. DoT and overall survival (OS) were estimated with the Kaplan-Meier method.
Over a period of 8 years and 3 months, n.161 patients were included: n.64 DTC, n.31 AdCC, n.41 HCC, and n.25 EC. Median follow-up (mFUP) was 72.8 months. Overall, median age at diagnosis was 61.8 years, with an ECOG PS 2 in 2%-9% of cases. The most frequently observed AE was fatigue. For the net of different cancer types, baseline BW/BMI, LEN doses, and mFUP, the BMI distribution was lower at last LEN administration compared to baseline ( = 0.045).
Despite the higher prevalence of elderly subjects and ECOG PS 2, our series confirmed the long-term manageability and effectiveness of LEN in the real world. Patients with a baseline low BMI require special attention, as LEN treatment can be implicated in further BW decrease.
仑伐替尼（LEN）是一种多激酶抑制剂，用于治疗不同肿瘤：进展期或对放射性碘耐药的分化型甲状腺癌（RAIR DTC）、涎腺腺样囊性癌（AdCC）、肝细胞癌（HCC）和子宫内膜癌（EC）。在现实世界中，符合使用仑伐替尼条件的患者通常有多种合并症和/或东部肿瘤协作组体能状态（ECOG PS）受损。在肝细胞癌中，体重（BW）<60 kg的患者需要较低的仑伐替尼起始剂量；在甲状腺癌（TC）中，体重对仑伐替尼的稳态暴露有临床相关影响。目前尚不清楚在仑伐替尼治疗期间，不同组织学类型患者的体重是否会发生变化。
本研究旨在调查毒性、治疗持续时间（DoT），并描述现实世界中患者体重和体重指数（BMI）的个体内变化。
在一家三级癌症中心进行的回顾性观察研究。
我们收集了2015年1月至2023年4月开始使用仑伐替尼治疗DTC、AdCC、HCC或EC的连续成年患者的临床特征和不良事件。将仑伐替尼的首次和末次剂量估计为每种适应症批准的标准剂量的百分比。用Mann-Whitney检验评估基线和治疗结束时评估的BMI分布差异。用Kruskal-Wallis检验评估患者内BMI变化的差异。用Kaplan-Meier方法估计治疗持续时间（DoT）和总生存期（OS）。
在8年零3个月的时间里，纳入了161例患者：64例DTC、31例AdCC、41例HCC和25例EC。中位随访时间（mFUP）为72.8个月。总体而言，诊断时的中位年龄为61.8岁，2%-9%的病例ECOG PS为2。最常观察到的不良事件是疲劳。在排除不同癌症类型、基线体重/体重指数、仑伐替尼剂量和中位随访时间的影响后，末次仑伐替尼给药时的BMI分布低于基线（P = 0.045）。
尽管老年患者和ECOG PS为2的患者比例较高，但我们的系列研究证实了仑伐替尼在现实世界中的长期可管理性和有效性。基线BMI较低的患者需要特别关注，因为仑伐替尼治疗可能导致体重进一步下降。
