Advancements Continue in HER2-Positive Breast Cancer

Over the past decade, the treatment landscape for HER2-positive breast cancer has continued to change, says Sara Hurvitz, M.D.

“I believe that a patient diagnosed today has a much greater chance of being alive five or 10 years from now — some of them may even be cured — and that compares very favorably with the outlook of 10 years ago when we just had one or two therapies and no evidence to support using HER2-targeted therapies after a patient’s disease grew,” Hurvitz said.

How far have we come in treating HER2-positive metastatic breast cancer?

In an interview with CURE, Hurvitz director of the Hematology/Oncology Breast Cancer Program and an associate professor in the Department of Medicine at the University of California, Los Angeles, discusses ongoing advances that continue to revolutionize the treatment of patients with HER2+ breast cancer.In terms of the metastatic setting, we have many different treatment options available now for patients. Just 10 years ago, when I started as a breast oncologist out of my fellowship, you had one opportunity to treat a patient with HER2-targeted therapy because we had no evidence and there was no approval for us to use Herceptin (trastuzumab) or Tykerb (lapatinib) after a patient’s disease grew on Herceptin b. Nowadays, we not only have Herceptin that we can use after a patient progresses, but we also have T-DM1, Tykerb, and dual HER2-targeting, as well as data to support us using endocrine therapy and HER2-targeted therapy.

Our treatment in the frontline setting has drastically changed with Herceptin and Perjeta (pertuzumab) with a taxane, with the longest median OS that has been reported in a clinical trial.

What are the current and emerging neoadjuvant treatment options?

I believe that a patient diagnosed today has a much greater chance of being alive five or 10 years from now — some of them may even be cured — and that compares very favorably with the outlook of 10 years ago when we just had one or two therapies and no evidence to support using HER2- targeted therapies after a patient’s disease grew.We are using a Herceptin plus Perjeta combination routinely for patients who need neoadjuvant therapy. That has become an FDA-approved, NCCN guideline-supported regimen because it gives the highest chance of a pCR.

The regimen I use most commonly is TCHP, which is docetaxel, carboplatin, Herceptin, and Perjeta, but there are two other regimens available in the United States based on the NeoSphere and TRYPHAENA studies. Those are either fluorouracil, epirubicin, and cyclophosphamide (FEC) for three cycles followed by docetaxel, Herceptin and Perjeta (THP) for three cycles, or THP times four cycles followed by surgery and then FEC after surgery for three cycles. That is the standard of care now. It gives patients a very high chance of having a complete eradication of their tumor, somewhere around 50 percent or higher in the breast and lymph nodes with the use of these therapies. We know that patients who achieve a pCR at the time of surgery have the most effective outcome. They are going to have the lowest chance of having their cancer come back and the most effective OS.

What are some of the most common adverse events with these treatments, and how do you manage them?

We did the KRISTINE study looking at T-DM1 and Perjeta compared with the TCHP regimen, hoping that the T-DM1 as a less toxic, more directed therapy would yield a better outcome, and it actually was inferior to standard chemotherapy. The pCR rate was lower for patients getting T-DM1, so it has not changed yet. Then, at the 2016 San Antonio Breast Cancer Symposium, Mothaffar Fahed Rimawi, M.D., presented the NSABP B-52 study looking at the TCHP regimen alone or in combination with endocrine therapy in patients with hormone receptor (HR)-positive/HER2-positive breast cancer. The trial showed high rates of pCR but no difference for patients who had endocrine therapy or not. Right now, there are a lot of ongoing studies looking at CDK4/6 inhibitors in combination with HER2-targeted therapies and other kinds of interesting combinations, but outside of a clinical trial the standard regimens are the ones I mentioned.With Herceptin and Perjeta combined we see higher rates of diarrhea and rash but Perjeta can be the cause of this. You just have to educate patients about that and have things like Imodium on hand and follow patients very closely. There are slightly higher rates of febrile neutropenia as well, so I am utilizing Neulasta (pegfilgrastim) prophylactically for patients getting chemotherapy plus dual HER2-targeted therapy. A lot of this is just education—patients being made aware of it and watching them closely.