Ten years' real-life experience on the use of multikinase inhibitors in patients with advanced differentiated thyroid cancer

Endocrine. 2024 Aug;85(2):817-826. doi: 10.1007/s12020-024-03867-4. Epub 2024 May 21.

Abstract

Purpose: To evaluate objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) associated with tyrosine kinase inhibitors (TKIs) in patients with radioiodine refractory differentiated thyroid cancer (RR-DTC). Additionally, to compare: (i) ORR and PFS among patients treated with lenvatinib and sorafenib; (ii) ORR and PFS among patients receiving lenvatinib as first-line vs. second-line and; (iii) adverse effects (AEs) observed in patients treated with these medications.

Methods: Retrospective analysis of RR-DTC adult patients treated with TKIs at the Division of Endocrinology, Hospital de Clinicas, University of Buenos Aires (March 2011-November 2023).

Results: Among 43 patients included in the study, 32 received sorafenib (30 as first-line and 2 as second-line), while 29 received lenvatinib (12 as first-line and 17 as second-line). The median PFS and OS for the entire cohort were 32.7 and 39.0 months, respectively. Lenvatinib demonstrated a significantly higher ORR compared to sorafenib (37.9% vs. 9.4%, p = 0.008). However, both drugs exhibited similar median PFS (23.2 vs. 16.0 months, p = 0.419). No significant difference was observed in ORR and PFS between patients receiving first-line vs. second-line lenvatinib. Sorafenib-treated patients experienced higher rates of hand-foot skin syndrome (69% vs. 41%, p = 0.032) and alopecia (25% vs. 3%, p = 0.018), whereas lenvatinib-treated patients had higher rates of proteinuria (31% vs. 0%, p < 0.001) and grade 3 hypertension (31% vs. 9%, p = 0.034).

Conclusion: TKIs demonstrated efficacy and tolerability comparable to real-world data in RR-DTC. PFS was not statistically different between sorafenib and lenvatinib. Our study will help guide physicians in making informed decisions regarding treatment sequencing with TKIs in these patients.

Keywords: Adverse events; Differentiated thyroid cancer; Lenvatinib; Progression-free survival; Sorafenib; Tyrosine kinase inhibitors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenylurea Compounds* / adverse effects
  • Phenylurea Compounds* / therapeutic use
  • Progression-Free Survival
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Quinolines* / adverse effects
  • Quinolines* / therapeutic use
  • Retrospective Studies
  • Sorafenib* / adverse effects
  • Sorafenib* / therapeutic use
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / pathology
  • Treatment Outcome

Substances

  • Phenylurea Compounds
  • lenvatinib
  • Protein Kinase Inhibitors
  • Sorafenib
  • Quinolines
  • Antineoplastic Agents