Late toxicities burden in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib

Endocrine. 2021 Sep;73(3):641-647. doi: 10.1007/s12020-021-02702-4. Epub 2021 Apr 2.

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusion: Late toxicity burden of lenvatinib is not negligible. Cardiovascular toxicity remains the principal side effect even after a prolonged lenvatinib exposition.

Keywords: Late toxicities; Lenvatinib; RAI-resistant; Thyroid cancer.

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Female
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Phenylurea Compounds / adverse effects
  • Protein Kinase Inhibitors / adverse effects
  • Quinolines* / adverse effects
  • Retrospective Studies
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / radiotherapy

Substances

  • Antineoplastic Agents
  • Iodine Radioisotopes
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Quinolines
  • lenvatinib