Utility and optimal management of planned drug holidays during lenvatinib treatment in patients with unresectable differentiated thyroid cancer: a real-world multi-center study

Endocrine. 2024 Aug;85(2):777-785. doi: 10.1007/s12020-024-03744-0. Epub 2024 Feb 27.

Abstract

Purpose: Lenvatinib achieves favorable therapeutic outcomes for patients with radioactive iodine therapy refractory differentiated thyroid cancer (DTC); however, its use is associated with a high incidence of adverse events. To avoid severe adverse events, planned drug holidays (PDH) have been proposed. This study aimed to evaluate treatment effects, identify prognostic factors, and investigate the usefulness of PDH in patients with unresectable DTC who received lenvatinib across the multi-institutions.

Methods: Fifty-one patients with unresectable DTC treated with lenvatinib were evaluated retrospectively. Overall survival (OS) and progression-free survival (PFS) were calculated, and prognostic factors were assessed. OS, PFS, and time to treatment failure (TTF) were compared between patients with and without PDH. Lenvatinib administration schedule was evaluated in PDH.

Results: The 3-year OS and PFS rate were 53.5% and 42.1%, respectively. Multivariate analysis revealed that presence of maximum size of lung metastasis ≥10 mm was independent prognostic factor for poorer OS and PFS, and histology other than papillary thyroid carcinoma was the independent prognostic factor for poorer PFS. Twenty-five patients (49%) treated with PDH. There were significant differences in OS, PFS, and TTF between patients with and without PDH. Various schedules were used in PDH. Eight (32%) patients required switch to the different administration schedule.

Conclusion: Our results suggest that PDHs may extend OS, PFS, and TTF. In patients with PDH, various schedules used for lenvatinib administration highlight the difficulty in determining a uniform administration schedule. Therefore, it is crucial to consider the optimal lenvatinib administration schedule on a case-by-case basis.

Keywords: Adverse events; Lenvatinib; Planned drug holidays; Prognosis; Thyroid cancer.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents* / administration & dosage
  • Antineoplastic Agents* / therapeutic use
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenylurea Compounds* / administration & dosage
  • Phenylurea Compounds* / adverse effects
  • Phenylurea Compounds* / therapeutic use
  • Prognosis
  • Quinolines* / administration & dosage
  • Quinolines* / adverse effects
  • Quinolines* / therapeutic use
  • Retrospective Studies
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / pathology
  • Treatment Outcome

Substances

  • lenvatinib
  • Quinolines
  • Phenylurea Compounds
  • Antineoplastic Agents