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

Context: Lenvatinib improved the progression-free survival (PPS) 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 lenvati nib (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 PPS (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.