famitinib and Hypothyroidism

Hypothyroidism is a common adverse event in patients treated with anti-VEGFR-2 targeting agents and may be a valuable predictive factor of efficacy. Famitinib is an inhibitor of multiple tyrosine kinases mainly targeting VEGFR-2. The objectives of this study were to assess the efficacy and safety of famitinib in patients with pretreated HER2-negative metastatic breast cancer (MBC) and to explore potential of famitinib-induced hypothyroidism and serum vascular endothelial growth factor (VEGF) level for efficacy prediction.. The primary end point was objective response rate (ORR). Famitinib was administered 25 mg/d. Thyroid function assessments were done at baseline and then every 4 weeks. Plasma levels of VEGF were determined at baseline and 2 cycles after treatment.. A total of 28 patients were enrolled. ORR was 14.3%. The most common grade 3/4 AEs were hand-foot syndrome (25.0%), proteinuria (21.4%) and hypertension (17.9%). 64.0% patients were observed with elevated thyroid-stimulating hormone (TSH) (>4.94 mIU/L) at any time during the entire treatment period. Sixteen patients with an elevated TSH had a significantly longer PFS than nine patients with no TSH elevation (107 vs. 53 days, respectively, P = 0.002). TSH elevation was also an independent predictor of PFS in a Cox regression model. Plasma VEGF levels did not correlate significantly with clinical outcomes.. Famitinib did show substantial anti-tumor activities with a good safety profile in heavily pretreated patients with HER2-negative MBC. Famitinib-related TSH increase may be an early indicator of its efficacy. Serial monitoring of serum TSH may help define VEGFR-2-dependent or VEGFR-2-independent drug resistance.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Female; Follow-Up Studies; Humans; Hypothyroidism; Indoles; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Pyrroles; Survival Rate; Thyrotropin; Vascular Endothelial Growth Factor Receptor-2; Young Adult