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

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.

Figures

Figure 1.

Maximum percentage change in sum of target lesion diameters from baseline in patients with RR-DTC who were randomized to receive lenvatinib in SELECT. Patients with best overall response of partial or complete response were considered responders. Patients whose earliest responses occurred within 30 days of receiving 24 mg/d lenvatinib were defined as responders at 24-mg lenvatinib; otherwise, patients were considered responders at less than 24-mg lenvatinib. Nonresponders shown include the 76 patients who had at least one postbaseline target lesion measurement.

Figure 2.

A, Change in tumor size over time (median and interquartile range of the percentage change in the sum of target lesion diameters) for patients with RR-DTC who were randomized to receive lenvatinib in SELECT. B, Percentage of lenvatinib-treated patients with observed nadir in tumor size over time. C, Change from baseline in Tg levels (median and SE) for lenvatinib-treated patients from SELECT. A straight dotted line is used to connect time points between 0 and 8 weeks because the real curve during this period is actually unknown. The connected lines are intended to highlight the general tumor shrinkage pattern over 88 weeks. The data are based on patients with both baseline and postbaseline tumor assessments. SE, standard error.

Figure 3.

A, Percentage change in tumor size at first postdose assessment and lenvatinib exposure during the first 8 weeks of treatment (at time of first tumor assessment). B, The relationship between lenvatinib treatment duration and maximum percentage tumor size change from baseline. AUC, area under the curve.

Figure 4.

Kaplan-Meier estimate of PFS of lenvatinib-treated patients with RR-DTC stratified by tumor size reduction (above vs below the median at wk 8, −24.7%).