Early Structural, Biochemical, and Metabolic Responses to Anlotinib in Patients With Progressive Radioactive Iodine Refractory Differentiated Thyroid Cancer

Objective We aimed to assess the early efficacy of anlotinib in progressive radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) patients in terms of structural, biochemical, and metabolic levels. Methods Ten eligible patients were prospectively enrolled to receive anlotinib. Six weeks' response were assessed. Apart from the structural response according to RECIST 1.1, biochemical response was assessed by serum thyroglobulin (Tg), metabolic response was assessed by 18 F-FDG PET/CT according to the EORTC criteria. Safety profile was recorded. Results Structurally controlled disease (20% partial response + 80% stable disease) was observed in all patients. The median longest diameter of target lesions shrank from 20.8 mm (IQR, 14.9 - 27.5) to 17.0 mm (IQR, 14.1 - 23.7) (P < 0.001), and the average shrinkage rate was -15.1 ± 14.1%. Sharp serum Tg reduction by 72.8 ± 16.4% was observed in eight measurable patients. 18 F-FDG PET/CT mapped glucose metabolic response was not quite comparable to structural response, with 90% of the patients held controlled disease (30% partial metabolic response + 60% stable metabolic disease), while 10% presented progressive metabolic disease. The most common treatment-emergent adverse events (AEs) were hypertension (100%) and proteinuria (70%). Most AEs were grade 1 or 2, while grade 3 AEs occurred only in hypertension. Conclusion Anlotinib is generally well tolerated and can bring early disease control within the initial six weeks of treatment. The sharp biochemical response suggests Tg as an early sensitive biomarker to anlotinib, while the heterogeneous metabolic response might play a complementary role.