Characterization of Tumor Size Changes Over Time From the Phase 3 Study of Lenvatinib in Thyroid Cancer

J Clin Endocrinol Metab. 2016 Nov;101(11):4103-4109. doi: 10.1210/jc.2015-3989. Epub 2016 Aug 22.

Abstract

Context: Lenvatinib improved the progression-free survival (PFS) and overall response rate of patients with radioiodine-refractory differentiated thyroid cancer vs placebo in the Phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT).

Objective: The objective of the study was to characterize tumor size changes with lenvatinib treatment.

Design: SELECT was a phase 3, randomized, double-blind, multicenter study.

Setting: In this clinical trial, tumor assessments of lenvatinib (n = 261) and placebo-treated (n = 131) patients were performed by independent radiological review per Response Evaluation Criteria in Solid Tumors version, 1.1 at 8-week intervals.

Patients: Patients with complete or partial response were defined as responders to lenvatinib (n = 169). Of the 92 nonresponders, 76 had at least one postbaseline tumor assessment and were included in this analysis.

Interventions: Lenvatinib (24 mg once daily) or placebo in 28-day cycles until unacceptable toxicity, disease progression, or death.

Main outcome measures: This was an exploratory analysis of key end points from SELECT, including PFS, overall response rate, and tumor reduction.

Results: The median maximum percentage change in tumor size was -42.9% for patients receiving lenvatinib (responders, -51.9%; nonresponders, -20.2%). Tumor size reduction was most pronounced at first assessment (median, -24.7% at 8 wk after randomization); thereafter, the rate of change was slower but continuous (-1.3% per mo). In a multivariate model, percentage change in tumor size at the first assessment was a marginally significant positive predictor for PFS (P = .06).

Conclusions: The change in tumor size conferred by lenvatinib was characterized by two phases: an initial, rapid decline, followed by slower, continuous shrinkage.

Trial registration: ClinicalTrials.gov NCT01321554.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / pharmacology*
  • Quinolines / administration & dosage
  • Quinolines / pharmacology*
  • Thyroid Neoplasms / diagnostic imaging*
  • Thyroid Neoplasms / drug therapy*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Quinolines
  • lenvatinib

Associated data

  • ClinicalTrials.gov/NCT01321554