Abstract P1-08-26: Hypertension and phosphorylated vascular endothelial growth factor receptor 2 are potential independent predictive factors for progession-free survival in apatinib-treated advanced breast cancer
Authors: Fan M , Hu X , Zhang J , Wang Z , Zhang Q 
Published: August 2014

Abstract
Background: Apatinib, one specific tyrosine kinase inhibitor that targets the VEGF receptor 2 was assessed in patients with advanced breast cancer. This substudy was to explore potential predictive and prognostic factors for apatinib-treated breast cancer.
Method: 80 patients were enrolled and received a starting dose of apatinib 750 or 500 mg/d in 4-week cycles. Efficacy was assessed according to RECIST 1.1 criteria, toxicity was graded based on the CTC adverse events version 4.0. The analyzed factors included patient-related factors, such as age; tumor-related factors, such as circulating biomarkers determined by multiplex cytokine assay and phosphorylated VEGFR2 by immunostaining; and treatment-related factors, such as adverse events. Cox Proportional Hazard model and Logistic test were performed as multivariate analysis to define the independent prognostic factors.
Result: Median PFS was 3.84 months, OS 10.64 months, with 17.5% of objective response rate.
Table 1. Efficacy summary No.PFS(months) 95% CIOS(months) 95% CIORR(%)CBR(%)Total803.84 (2.66, 5.03)10.64 (8.55, 12.73)17.537.5TNBC604.30 (2.83, 5.77)9.23 (5.69, 12.77)2041.67non-TNBC203.34 (2.05, 4.63)10.66 (10.38, 10.95)1025P value 0.2110.6700.4990.286
The most frequent adverse events were hypertension (66.3% for all grades, 17.5% for grade 3/4), hand-foot skin reaction (HFSR, 62.5% for all grades, 20% for grade 3/4), and proteinuria (61.3% for all grades, 7.5% for grade 3/4). According to univariate analysis, longer PFS was correlated with hypertension (p = 0.011), HFSR (p = 0.018), post-menopause (p = 0.021), less previous chemotherapy (p = 0.021), higher drug trough concentration (p = 0.025), and higher baseline serum sVEGFR2 (p = 0.031). Median PFS was 6.60 and 2.00 m in patients with higher and lower p-VEGFR2 expressions (p = 0.001). According to multivariate regression analysis, hypertension (p = 0.038; HR, 0.583, 95% CI 0.351 - 0.969) and p-VEGFR2 expression level (p = 0.013; HR, 0.404, 95% CI 0.198 - 0.826) were independent predictive factors of PFS.
Table 2. Summary of univariate analysisFactorsHR (95% CI)Hypertension, with / without0.4856(0.2794 - 0.8442)Hand-foot skin reaction, with / without0.5337(0.3178-0.8963)Proteinuria, with / without0.7887(0.4896-1.270)Fatigue, with / without0.6540 (0.4113-1.040)Age ≥ 60y / &lt; 60y0.5591(0.3101-1.008)Menstruation status, pre / post0.5321(0.3111- 0.9102)ECOG = 0 / ECOG = 10.8989(0.5688-1.421)TNBC / non-TNBC0.6904(0.3863-1.234)DFI ≥ 12m / &lt; 12m0.7114(0.4436-1.141)Visceral metastasis, yes / no0.7999(0.4800-1.333)No. of metastasis site, ≥ 3 / &lt; 31.276(0.7773-2.096)Lines of prior chemothyrapy, ≥ 2 / &lt; 21.792(1.094-2.935)Tumor markers, elevated / normal1.437(0.8507-2.426)sVEGFR2, high / low0.4111(0.1829-0.9239)VEGFR2, high / low0.5112(0.2243-1.165)p-VEGFR2, high / low0.2544(0.1117-0.5796)Hazard ratios for each factor
Conclusion: Apatinib showed substantial antitumor activity in patients with heavy-pretreated advanced breast cancer with manageable toxicity. Hypertension and p-VEGFR2 were independent predictive factors for PFS in apatinib-treated advanced breast cancer, and significantly correlated to higher CBR.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-26.