Anlotinib in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma: A Randomized, Double-Blind, Multicenter Phase II Trial.

PURPOSE

Alhough antiangiogenic agents are the bedrock of treatment for radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), novel antiangiogenic agents with optimized features like greater target-binding affinities and more favorable pharmacokinetics profile are needed. This phase II randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of anlotinib, a multikinase inhibitor, for RAIR-DTC.

PATIENTS AND METHODS

Patients (ages between 18 and 70 years) with pathologically confirmed locally advanced or metastatic RAIR-DTC were enrolled and randomly received 12 mg anlotinib once daily or placebo on day 1 to 14 every 3 weeks. Patients on placebo were allowed to receive open-label anlotinib after disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and safety.

RESULTS

Between September 2015 and August 2018, 76 and 37 patients randomly received anlotinib and placebo, respectively. Patients receiving anlotinib had a significantly longer median PFS [40.5 months, 95% confidence interval (CI), 28.3-not estimable (NE) versus placebo 8.4 months, 95% CI, 5.6-13.8; HR = 0.21, 95% CI, 0.12-0.37, P < 0.001], meeting the primary endpoint. OS was still immature, with a trend of benefit with anlotinib (HR = 0.57, 95% CI, 0.29-1.12). All patients in the anlotinib group experienced adverse events (AE); 8 (10.5%) discontinued treatment due to AEs.

CONCLUSIONS

Anlotinib demonstrated promising efficacy and favorable tolerance in the treatment of locally advanced or metastatic RAIR-DTC, supporting further research to establish its role in the treatment of this serious disease.