Lenvatinib in advanced thyroid, salivary gland, endometrial, and hepatocellular carcinomas: a real-world study on treatment duration and toxicity management.

Background: 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. Objectives: 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. Design: Retrospective observational study conducted in a tertiary cancer center. Methods: 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. Results: 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 ( Conclusion: 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.