A Randomized, Phase III Study of Lenvatinib in Chinese Patients with Radioiodine-Refractory Differentiated Thyroid Cancer

Abstract

Purpose: Lenvatinib has shown efficacy in treating radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the multinational phase III SELECT study; however, it has not been tested in Chinese patients with RR-DTC.

Patients and methods: Chinese patients with confirmed RR-DTC (n = 151) were randomly assigned 2:1 to receive lenvatinib 24 mg/day or placebo in 28-day cycles. The primary endpoint was progression-free survival, and key secondary endpoints included objective response rate and safety. Analyses for progression-free survival and objective response rate were conducted using Response Evaluation Criteria in Solid Tumors v1.1 and confirmed by independent imaging review. All adverse events were assessed and monitored.

Results: Progression-free survival was significantly longer with lenvatinib treatment [n = 103; median 23.9 months; 95% confidence interval (CI), 12.9-not estimable] versus placebo (n = 48; median 3.7 months; 95% CI, 1.9-5.6; hazard ratio = 0.16; 95% CI, 0.10-0.26; P < 0.0001). The objective response rate was 69.9% (95% CI, 61.0-78.8) in the lenvatinib arm and 0% (95% CI, 0-0) in the placebo arm. At data cutoff, 60.2% of patients receiving lenvatinib remained on treatment; treatment-emergent adverse events led to lenvatinib discontinuation in 8.7% of patients. Overall, treatment-emergent adverse events of grade ≥3 occurred in 87.4% of patients in the lenvatinib arm, the most common being hypertension (62.1%) and proteinuria (23.3%).

Conclusions: Lenvatinib at a starting dose of 24 mg/day significantly improved progression-free survival and objective response rate in Chinese patients with RR-DTC versus placebo. There were no new or unexpected toxicities. Results are consistent with those from SELECT involving patients with RR-DTC.

Trial registration: ClinicalTrials.gov NCT02966093.

©2021 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.

Patient enrollment, randomization, and treatment.

Figure 2.

Kaplan–Meier plot of PFS as assessed by IIR using RECIST v1.1. There were 2 patients censored following discontinuation of study drug owing to an AE, both in the lenvatinib arm. Of these, 1 patient experienced dysphagia that was considered by the investigator to be not related to lenvatinib and 1 patient experienced dyspnea that was considered by the investigator to be related to lenvatinib. AE, adverse event; CI, confidence interval; HR, hazard ratio; IIR, independent imaging review; NE, not estimable; PFS, progression-free survival; RECIST v1.1, Response Evaluation Criteria In Solid Tumors version 1.1.

Figure 3.

Percentage changes in the sums of diameters of target lesions from baseline to postbaseline nadir for patients treated with (A) lenvatinib or (B) placebo (by IIR using RECIST v1.1). CR, complete response; IIR, independent imaging review; NE/UNK, not evaluable/unknown; PD, progressive disease; PR, partial response; RECIST v1.1, Response Evaluation Criteria In Solid Tumors version 1.1; SD, stable disease. aTwo patients were determined to be PD due to nontarget lesions, but target lesions were not evaluable. These patients are not depicted on the plot. b“Unknown” patients lacked a baseline and/or postbaseline tumor assessment. c1 patient had a single postbaseline assessment at week 5 but this duration was not long enough to be considered SD. This patient is considered “NE” and is shown in gray in this plot.