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

Abstract

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). The objective of the study was to characterize tumor size changes with lenvatinib treatment. SELECT was a phase 3, randomized, double-blind, multicenter study. 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 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. Lenvatinib (24 mg once daily) or placebo in 28-day cycles until unacceptable toxicity, disease progression, or death. This was an exploratory analysis of key end points from SELECT, including PFS, overall response rate, and tumor reduction. 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). The change in tumor size conferred by lenvatinib was characterized by two phases: an initial, rapid decline, followed by slower, continuous shrinkage.