An update on biomarkers of potential benefit with bevacizumab for breast cancer treatment: Do we make progress?

Xu Liang,Florence Lerebours,Huiping Li,Florence Coussy,Celine Callens

doi:10.21147/j.issn.1000-9604.2019.04.03

Abstract

As the first monoclonal antibody against vascular endothelial growth factor (VEGF), bevacizumab (BEV) is a definitely controversial antiangiogenic therapy in breast cancer. The initial excitement over improvements in progression-free survival (PFS) with BEV was tempered by an absence of overall survival (OS) benefit and serious adverse effects. Missing targeted population urged us to identify the predictive biomarkers for BEV efficacy. In this review we focus on the research in breast cancer and provide recent investigations on clinical, radiological, molecular and gene profiling markers of BEV efficacy, including the new results from randomized phase III clinical trials evaluating the efficacy of BEV in combination with comprehensive biomarker analyses. Current evidences indicate some predictive values for genetic variants, molecular imaging, VEGF pathway factors or associated factors in peripheral blood and gene profiling. The current challenge is to validate those potential biomarkers and implement them into clinical practice.

Highlights

The addition of bevacizumab (BEV) to chemotherapy for metastatic breast cancer (MBC) was first proposed a decade ago
This study suggested that expression of delta-like ligand 4 (Dll4), vascular endothelial growth factor (VEGF)-C and neuropilin-1 (NRP1) showed trends toward improvement in progression-free survival (PFS) associated with the addition of BEV
A phase II study of neoadjuvant BEV followed by combination of BEV and chemotherapy in human epidermal growth factor receptor 2 (HER2)-negative BC has found pretreatment microvascular density (MVD) as a potential predictive biomarker of response to BEV in BC [47]. This trial showed a higher rate of pathological complete response (pCR) in triple-negative breast cancer (TNBC) than in hormone receptor-positive (HR) BC that results from greater baseline MVD in TNBC compared to HRBC

Summary

Introduction

The addition of bevacizumab (BEV) to chemotherapy for metastatic breast cancer (MBC) was first proposed a decade ago. BEV, bevacizumab; Doc, docetaxel; PTX, paclitaxel; Tras, trastuzumab; NVB, vinorelbine; CTX, cyclophosphamide; MBC, metastatic breast cancer; LABC, locally advanced breast cancer; TNBC, triple negative breast cancer; VEGF, vascular endothelial growth factor; pVEGF-A, plasma VEGF-A; EGFR, epidermal growth factor receptor; sVEGFR, soluble vascular endothelial growth factor receptor; ICAM-1, intracellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule 1; MMP, matrix metalloproteinases; Ang II, angiopoietin-2; sTie, receptor tyrosine kinases 2; PlGF, placental growth factor; bFGF, basic fibroblast growth factor; IL, interleukin; TNF-α, tumor necrosis factor alpha; SDF1α, stromal cell-derived factor α; CAIX, carbonic anhydrase 9; IGF-1, insulin-like growth factor 1; CCL, chemokine (C-C motif) ligand; DFS, disease-free survival; OS, overall survival; PFS, progression-free survival; TTP, time to treatment failure; *, Number of patients in sub study/parent trial. BR-211A and BR- Neoadjuvant 211B: phase II, BEV breast cancer or Tras or nabpaclitaxel (single dose) followed BEV + nab-paclitaxel + CBP or Tras + nabpaclitaxel + CBP

44 RNA sequencing

Findings

Conclusions