Associations between plasma concentrations of lenvatinib and angiopoietin and clinical responses to lenvatinib therapy in Japanese patients with thyroid cancer

Abstract The purpose of this study was to investigate the relationships among plasma concentrations (C 0 ) of lenvatinib, angiopoietin (Ang)-1 and Ang-2, and clinical responses to lenvatinib therapy in thyroid cancer patients. The median change rates of Ang-1 and Ang-2 at 1 month after treatment from baseline in all patients were − 15.3% and − 48.4%, respectively. However, the change of Ang-1 and Ang-2 at 1 month from baseline did not correlate with lenvatinib C 0 . In patients with partial response (PR) and stable disease to lenvatinib, Ang-2 at 1 month were significantly lower than Ang-2 at baseline ( P < 0.001 and P < 0.05, respectively), but were not significantly lower in patients with progressive disease. The area under the ROC for PR prediction was 0.667, giving the best sensitivity (69.2%) and specificity (73.9%) at a threshold of the change rate of Ang-2 of -49.83%. In patients who continued treatment with lenvatinib for 1 year, Ang-2 at 1 month and 1 year were significantly lower than those at baseline (each P < 0.001). The change of Ang-2 at 1 month after treatment from baseline rather than simply the Ang-2 level at baseline may be important as a biomarker of the inhibitory effect of angiogenesis by lenvatinib.