Patients with locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma demonstrated a statistically significant progression-free survival benefit when treated with anlotinib, a novel tyrosine kinase inhibitor, vs placebo, as well as higher response rates, according to findings from a phase II study presented by Chi et al at the ESMO Asia Virtual Congress 2020 (Abstract 2650).

Researchers described anlotinib as a new, orally administered tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit.

Single-agent anlotinib was granted approval by the China Food and Drug Administration in May 2018 as a third–line treatment for patients with advanced non-small cell lung cancer.

Trial Details

The research team carried out a randomized, double-blind, placebo-controlled, multicenter phase II study evaluating anlotinib for the treatment of radioiodine-refractory differentiated thyroid carcinoma. The study enrolled patients aged 18 to 70 years old with measurable, pathologically confirmed locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma who had not received prior treatment with anlotinib or other VEGFR tyrosine kinase inhibitors.

Following 2:1 random assignment, 76 patients were treated with anlotinib at 12 mg daily for 2 weeks followed by 1 week off, and 37 patients received placebo. 

The primary endpoint was progression-free survival; secondary endpoints included objective response rate, disease control rate, overall survival, and safety. Patients in the placebo arm were allowed to cross over to open-label anlotinib upon disease progression.

Findings

At data cutoff in January 2020, median progression-free survival was 40.54 months (95% confidence interval [CI] = 28.29–not estimated) with anlotinib compared to 8.38 months (95% CI = 5.59–13.80) with placebo (hazard ratio [HR] = 0.21, 95% CI = 0.12–0.37, P < .0001).

Whereas no response was seen in the placebo arm, patients receiving anlotinib demonstrated an objective response rate of 59.21% (P < .0001). Disease control differed significantly between the groups: patients on anlotinib showed a disease control rate of 97.37% compared to 78.38% among those treated with placebo (P = .002).

The overall survival data are not yet mature.

All patients receiving anlotinib and 97.30% of patients on placebo experienced adverse events (P = .327), and the incidence of treatment-related adverse events was 100.00% vs 86.49%, respectively (P = .003). The most commonly reported adverse events with anlotinib were hypertension in 84.21% and hand-foot syndrome in 73.68% of patients. Serious treatment-related adverse events occurred in 15.79% of patients receiving anlotinib.

The authors concluded that findings from this study demonstrated the efficacy and safety of anlotinib and support the use of anlotinib as a new option for the treatment of locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma.

Disclosure: This study was funded by the Chia Tai Tian Qing Pharmaceutical Group Co., Ltd. For full disclosures of the study authors, visit oncologypro.esmo.org.