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Hamilton Highlights Treatment Landscape of HER2+ Breast Cancer

Danielle Bucco
Published: Thursday, Dec 28, 2017

Erika P. Hamilton, MD
Erika P. Hamilton, MD
Patients with HER2-positive breast cancer no longer have as poor of a prognosis due to the development of numerous HER2-directed therapies, explains Erika P. Hamilton, MD.

For example, the December 2017 FDA approval of pertuzumab (Perjeta) in the adjuvant space, which was based on the phase III APHINITY trial, gives another treatment option. Adjuvant treatment with pertuzumab, trastuzumab (Herceptin), and chemotherapy demonstrated a 3-year invasive disease-free survival rate of 94.1% versus 93.2% for those who received trastuzumab plus chemotherapy and placebo. This represented an 18% reduction in the risk of developing invasive disease or death (HR, 0.82; 95% CI, 0.67-1.00; P = .047).

In an interview with OncLive, Hamilton, director of the Breast and Gynecologic Research Program at Sarah Cannon Research Institute, discussed recent FDA approvals in the treatment paradigm of HER2-positive breast cancer and shed light on the prevalence of brain metastases.

OncLive: If a patient undergoes testing and it comes back that they have HER2 expression, what are some of the first things you are thinking about when determining treatment?

Hamilton: We know that HER2-positive breast cancers are more aggressive and tend to grow quicker. However, we now have HER2-directed therapies that make this disease not as poor of a prognosis as it used to be. In many ways, we all dread triple-negative breast cancer much more than HER2-positive breast cancer now, with the advent of improved HER2-targeted agents that have improved outcomes significantly. 

When someone is initially diagnosed with HER2-positive breast cancer, we want to know if we are in the curative or non-curative space. We are then thinking about a chemotherapy backbone in combination with a HER2-directed agent, such as trastuzumab and pertuzumab.

Can you discuss what impact the recent FDA approval of pertuzumab will have on this patient population?

It is exciting that we now have the adjuvant approval. Pertuzumab has been approved in the metastatic and neoadjuvant setting for some time and medical oncologists have been trying to capture those patients before they go to surgery to give them pertuzumab in the neoadjuvant setting. However, sometimes patients go to surgery without seeing a medical oncologist, when their cancer is easily resectable, and they didn’t have the ability to receive pertuzumab after surgery since it hasn’t been approved in the adjuvant setting. It takes the pressure off now that pertuzumab is approved across the board.

Its uptake in the adjuvant space is probably not going to be, nor should it be, 100%. We are learning that there are different subsets of patients that need pertuzumab more than others. Right now, it looks like those 2 subsets are probably the node-positive patients and/or the patients who are also of hormone receptor–negative status. 

Can you discuss the sequencing of agents?

In the neoadjuvant space for patients who are high risk, have a tumor greater than 2 centimeters, or have node-positive disease, we are using a regimen of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). In the adjuvant space, we now can use pertuzumab in conjunction with trastuzumab after this approval.

The metastatic setting is where sequencing comes in. It is tricky and will be changing over the next couple of years as more patients receive pertuzumab in the early-stage setting. Currently, our standard algorithm in the first-line setting is paclitaxel, trastuzumab, and pertuzumab (THP). In the second-line space, people receive ado-trastuzumab emtansine (T-DM1; Kadcyla). Third-line and beyond is open as there are many different options and not one standard of care. However, for the patients in the neoadjuvant and adjuvant space who are quickly relapsing on pertuzumab, we likely will not treat those patients with pertuzumab again. We will probably be bringing T-DM1 up. 

This opens the way for new HER2-targeted agents in the second-line and beyond. There are many clinical trials investigating new HER2 compounds.

Can you discuss those emerging HER2 compounds?

One of the things that has been exciting for HER2-positive breast cancer is T-DM1. It is our first antibody-drug conjugate for breast cancer. That is essentially where your chemotherapy is bound or fused together with an antibody. How I like to explain this to patients is it is not “naked chemotherapy.” I call it “naked chemotherapy” when it is infused in the veins and goes everywhere in your body, which can cause adverse events (AEs) in other cells such as hair loss, damage to our infection fighting cells or nerves, or nausea.

There are a lot of new antibody-drug conjugates in development. There are also new HER2 antibodies, similar to pertuzumab. There are new ways to target HER2 in a stronger way than we have thought about before. 

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