Phosphorylated VEGFR2 and hypertension: potential biomarkers to indicate VEGF-dependency of advanced breast cancer in anti-angiogenic therapy

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• 作者：Minhao Fan (1)
  Jian Zhang (1)
  Zhonghua Wang (1)
  Biyun Wang (1)
  Qunlin Zhang (1)
  Chunlei Zheng (1)
  Ting Li (1)
  Chen Ni (1)
  Zhenhua Wu (1)
  Zhimin Shao (2) (3)
  Xichun Hu (1) (3)
  
• 关键词：Tyrosine kinase inhibitor (TKI) ; Biomarker ; Advanced breast cancer (ABC) ; VEGF ; dependency ; Apatinib
• 刊名：Breast Cancer Research and Treatment
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：143
• 期：1
• 页码：141-151
• 全文大小：888 KB
• 作者单位：Minhao Fan (1)
  Jian Zhang (1)
  Zhonghua Wang (1)
  Biyun Wang (1)
  Qunlin Zhang (1)
  Chunlei Zheng (1)
  Ting Li (1)
  Chen Ni (1)
  Zhenhua Wu (1)
  Zhimin Shao (2) (3)
  Xichun Hu (1) (3)
  
  1. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
  2. Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
  3. Department of Oncology, Shanghai Medical College, Fudan University, No. 270, Dong’an road, Shanghai, 200032, China
  
• ISSN：1573-7217

文摘

The efficacy of anti-VEGF agents probably lies on VEGF-dependency. Apatinib, a specific tyrosine kinase inhibitor that targets VEGF receptor 2, was assessed in patients with advanced breast cancer (ABC) (ClinicalTrials.gov NCT01176669 and NCT01653561). This substudy was to explore the potential biomarkers for VEGF-dependency in apatinib-treated breast cancer. Eighty pretreated patients received apatinib 750 or 500?mg/day orally in 4-week cycles. Circulating biomarkers were measured using a multiplex assay, and tissue biomarkers were identified with immunostaining. Baseline characteristics and adverse events (AEs) were included in the analysis. Statistical confirmation of independent predictive factors for anti-tumor efficacy was performed using Cox and Logistic regression models. Median progression-free survival (PFS) was 3.8?months, and overall survival (OS) was 10.6?months, with 17.5?% of objective response rate. Prominent AEs (?0?%) were hypertension, hand-foot skin reaction (HFSR), and proteinuria. Higher tumor phosphorylated VEGFR2 (p-VEGFR2) expressions (P?=?0.001), higher baseline serum soluble VEGFR2 (P?=?0.031), hypertension (P?=?0.011), and HFSR (P?=?0.018) were significantly related to longer PFS, whereas hypertension (P?=?0.002) and HFSR (P?=?0.001) were also related to OS. Based on multivariate analysis, only p-VEGFR2 (adjusted HR, 0.40; P?=?0.013) and hypertension (adjusted HR, 0.58; P?=?0.038) were independent predictive factors for both PFS and clinical benefit rate. Apatinib had substantial antitumor activity in ABC and manageable toxicity. p-VEGFR2 and hypertension may be surrogate predictors of VEGF-dependency of breast cancer, which may identify an anti-angiogenesis sensitive population.