Biomarker May Predict Efficacy of Bevacizumab in HER2-Negative Tumors

Precision medicine continues to make inroads in treating patients with cancer in a specific, rather than broad manner, and new evidence demonstrates greater efficacy in predicting which patients will benefit from a targeted therapy.

Bevacizumab (Avastin), a monoclonal antibody first approved by the US Food and Drug Administration (FDA) in 2004 for treating colorectal cancers, has shown to be effective in treating several other cancer types, including HER2-negative breast cancer as of 2008.¹ A new finding shows that a biomarker may predict which patients would benefit most from this treatment.

When bevacizumab was first rolled out to treat metastatic HER2-negative breast cancer tumors, not all patients' tumors responded, leading the FDA to recall its initial approval of its usage in this setting in 2011. But now, because of the new findings regarding the biomarker, oncologists are better able to discern which patients will benefit from this therapy.

This was first reported in the International Journal of Cancer.²

This is an important finding for several reasons. Aside from treatment efficacy, this new finding could spare patients the severe toxicity associated with bevacizumab that benefits some, but not all.

“What all this means is that we have identified a signature that tells us which patients are likely to respond to bevacizumab and chemotherapy,” said Principal Investigator and senior author Lyndsay Harris, MD, Professor of Medicine at Case Western Reserve in Cleveland, in a press release. “And we can identify those patients within 15 days of the very first dose they receive.”³

Researchers assessed tumor tissue from HER2-negative patients at baseline prior to administration of bevacizumab, and then patients received a single dose of bevacizumab. After 10 to 14 days, tumor tissue was collected to examine molecular changes that occurred in the tumor in response to bevacizumab. The researchers found a significant decrease in TGF-beta signaling activity, a process that affects cell proliferation, which occurs exclusively in tumors that achieve a complete response (CR). This finding is associated with a more than 90% cure rate for that patient and is likely due to decreases in hypoxia--state of low oxygen--in the tumor cells that makes them more treatable.³

“Our finding is not so much about the single drug,” said Harris. “What matters most is we can identify biomarkers to help us select therapy properly. In our study, we have found this signature to be specifically useful in response to bevacizumab, but it may be useful in predicting response to other antiangiogenic agents as well and should be tested.”³

This crucial finding may enable practicing oncologists to again use this treatment if the FDA approves the usage in this clinical setting.

References:

• US Food and Drug Administration (FDA). (2011). Avastin (bevacizumab) Information.
• Varadan V, Kamalakaran S, Gilmore H, et al. (2015). Brief-exposure to preoperative bevacizumab reveals a TGF-β signature predictive of response in HER2-negative breast cancers. International Journal of Cancer, Aug 18. doi: 10.1002/ijc.29808.
• Case Western Reserve School of Medicine. (2015). Biomarker may predict which HER2-negative breast cancer patients will benefit from targeted therapy.