Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer

Eur J Cancer. 2021 Apr:147:51-57. doi: 10.1016/j.ejca.2020.12.032. Epub 2021 Feb 19.

Abstract

Background: Lung metastases may worsen overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). We investigated (post hoc) the impact of lung metastases on survival in SELECT (a phase 3 study).

Patients and methods: 392 patients with RR-DTC were randomised 2:1 to lenvatinib 24 mg daily (n = 261) or placebo (n = 131). Placebo-treated patients could crossover to open-label lenvatinib following progression. Patients were grouped by size of baseline lung metastases. Safety/efficacy outcomes, collated by these lung-metastases subgroups, were generated.

Results: Lenvatinib-treated population distributions per baseline lung metastases subgroup were any lung metastases (target/nontarget lesions; n = 226), and by maximum size of target lung lesions ≥1.0 cm (n = 199), ≥1.5 cm (n = 150), ≥2.0 cm (n = 94) and <2.0 cm (n = 105). In patients with any lung metastases, no statistically significant difference in OS was observed between treatment arms (HR: 0.76; 95% CI: 0.57-1.01; P = 0.0549). Median OS for lung metastases of ≥1.0 cm was 44.7 months (lenvatinib) versus 33.1 months (placebo) (HR: 0.63; 95% CI: 0.47-0.85; P = 0.0025). OS was significantly prolonged with lenvatinib versus placebo among patients with lung metastases of ≥1.0 cm, ≥1.5 cm, ≥2.0 cm and <2.0 cm; median OS was shorter in the ≥2.0 cm subgroup (lenvatinib: 34.7 months) versus other subgroups (lenvatinib: 44.1-49.2 months). Multivariate analysis demonstrated lenvatinib significantly prolonged OS in patients with lung metastases of ≥1.0 cm after adjustment for baseline characteristics.

Conclusions: Lenvatinib treatment resulted in longer OS in patients with lung metastases of ≥1.0 cm versus placebo (even with the 89% crossover rate). Early initiation of lenvatinib may improve outcomes in patients with RR-DTC and lung metastases of ≥1.0 cm.

Source study registration: ClinicalTrials.Gov Identifier: NCT01321554.

Keywords: Lenvatinib; Lung metastases; Overall survival; RR-DTC; Radioiodine-refractory differentiated thyroid cancer.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Cell Differentiation
  • Double-Blind Method
  • Female
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • 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*
  • Radiation Tolerance
  • Radiopharmaceuticals / therapeutic use
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology
  • Time Factors
  • Tumor Burden

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01321554