Abstract P2-09-18: High VEGFR1 and VEGFR3 Protein Expression Is Associated with Improved Response to the Combination of Paclitaxel (P) and Bevacizumab (Bev) Therapy in Patients with HER2-Negative Metastatic Breast Cancer (MBC)

Background: Treatment with weekly P and 2-weekly Bev has been established as an active 1 st line treatment in patients with MBC. However, robust predictive or prognostic biomarkers for this treatment have not been identified as yet. Patients and Methods: In this retrospective analysis, we evaluated the activity of this combination in patients with HER2-negative MBC. Further, we explored the role of a panel of biomarkers on patients’ outcome. VEGF-A, VEGF-C, VEGFR1, VEGFR2, and VEGFR3 were centrally assessed by immunohistochemistry (IHC) in 70 tissue blocks. P was administered either weekly 90 mg/m 2 x12 with 2-weekly Bev 10 µg/kg (86 patients) or 3-weekly 175 mg/m 2 x6 with 3-weekly Bev 15µg/kg (38 patients). Bev was administered until progression in the majority of the patients. Results: The ORR did not differ significantly between the weekly or 3-weekly P schedule (55.8% vs 55.3%). In contrast to the published literature with P monotherapy, median PFS was significantly longer in the 3-weekly compared to the weekly P schedule (20.4 months vs 10.2 months, p=0.029). Median survival has not been reached yet. 2-year survival was 76.1% and 67.3%, respectively (p=0.085). High VEGFR1 and VEGFR3 protein expression, assessed by IHC, was associated with higher response rates (p=0.010 and p=0.039, respectively). Conclusions: This retrospective analysis confirmed the activity of P and Bev in patients with HER2-negative MBC. Protein expression of VEGFR1 and VEGFR3 was found to be of predictive value. These findings need to be validated in a larger cohort of patients treated with this combination. VEGF polymorphisms (VEGF-2578 and VEGF-1154) are currently assessed in peripheral blood DNA from our patients for possible predictive value. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-18.