Prior exposure to chemotherapy: a marker of sensitivity and selection for antiangiogenic therapy in breast cancer?

Abstract

The identification of patients who are more likely to derive benefit from antiangiogenic therapy is a key to refine patient selection and so maximize clinical benefit, and reduce unnecessary treatment costs. Improved patient selection will equally be effective in minimizing the exposure of non-eligible patients to ineffectual treatment which could be associated with adverse effects as well as delaying effective treatment. Herein, we review the literature from clinical trials suggesting that the addition of antiangiogenic agents to chemotherapy for the treatment of HER-2 negative metastatic breast cancer in patients previously exposed to chemotherapy may deliver differential therapeutic benefit and may serve as a selection criteria in the current absence of a robust biomarker.

Keywords::

• angiogenesis
• axitinib
• bevacizumab
• breast cancer
• rechallenge
• taxane

Financial & competing interests disclosure

C. Palmieri wishes to acknowledge the funding support from Cancer Research UK. The Liverpool Cancer Trials Unit receives funding from Cancer Research UK, and the Department of Molecular and Clinical Cancer Medicine, forms part of the Liverpool Cancer Research UK Centre which is funded by Cancer Research UK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Angiogenesis is a critical feature of tumorogenesis.

• VEGF is a key mediator of angiogenesis and is currently the target of a number of therapies both monoclonal antibody (mAb) and tyrosine kinase inhibitors (TKIs).

• To date only bevacizumab with paclitaxel or docetaxel have shown benefit compared to control.

• Identifying patients that may derive differential benefit from antiangiogenic therapy is key to maximize clinical benefit, avoiding unnecessary toxicity and to ensure optimal utilization of resources.

• VEGF-A is currently the lead biomarker for the selection of patients for treatment with bevacizumab, and its utility with this regard is currently being tested in the context of a clinical trial.

• Unplanned subgroup analysis and exploratory meta-analysis with bevacizumab, as well with axitinib suggest that patients with prior adjuvant chemotherapy derived differential benefit from antiangiogenic therapy.

• The nature of current data given suggests that it requires testing in the context of randomized studies with relevant translational end-points including VEGF-A levels.