Long-Term Results of a Phase II Trial of Apatinib for Progressive Radioiodine Refractory Differentiated Thyroid Cancer

Context Radioiodine refractory differentiated thyroid cancer (RAIR-DTC) has been a global challenge due to its poor prognosis and limited treatment options. Objective We report here the long-term results of the phase II clinical trial of apatinib, an anti-angiogenic tyrosine kinase inhibitor, for RAIR-DTC. Methods This was an open-label, exploratory phase II clinical trial among progressive RAIR-DTC patients. Apatinib treatment was given once daily until disease progression, unmanageable toxicity, withdrawal, or death. The primary end points were objective response rate (ORR) and disease control rate (DCR). Progression-free survival (PFS), overall survival (OS), duration of response, long-term safety, and the association between patients with different tumor genotype (BRAFV600E and TERT promotor mutation) and their PFS rates were also assessed. Results The ORR was 80%, and the DCR was 95%. The overall median PFS was 18.4 months (95% CI, 9.2-36.8 months) and the median OS was 51.6 months (95% CI, 29.2-not reached [NR]). Patients with BRAFV600E mutation (10 of 18 evaluated) had a longer median PFS compared with patients with BRAF wild-type (NR vs 9.2 months; P = 0.002). The most common adverse events included palmar-plantar erythrodysesthesia syndrome (19/20), proteinuria (18/20), and hypertension (16/20). Conclusion In this long-term evaluation, apatinib displayed sustainable efficacy and tolerable safety profile, warranting it as a promising treatment option for progressive RAIR-DTC.