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Cancer Chemother Pharmacol. 2014 Aug;74(2):389-98. doi: 10.1007/s00280-014-2505-x. Epub 2014 Jun 18.

Hypothyroidism as a potential biomarker of efficacy of famitinib, a novel VEGFR-2 inhibitor in metastatic breast cancer.

Author information

1
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Fudan University Cancer Hospital, Shanghai Medical School, No. 270, Dong'an Road, Shanghai, 200032, China.

Abstract

PURPOSE:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01653574.

PMID:
24939214
DOI:
10.1007/s00280-014-2505-x
[Indexed for MEDLINE]
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