Neoadjuvant Treatment Evolving in HER2-Positive Breast Cancer

Elizabeth A. Mittendorf, MD, PhD

The role of neoadjuvant therapy for patients with HER2-positive breast cancer continues to evolve, including ongoing efforts to determine which patients are likely to respond to the early treatment.

For example, an ongoing phase II clinical trial is assessing whether early changes on a PET imaging procedure will predict which patients are most likely to respond to the combination of pertuzumab (Perjeta) and trastuzumab (Herceptin) prior to surgery for patients with HER2-positive breast cancer (NCT01937117). The experimental arm will investigate the response to preoperative treatment with trastuzumab and pertuzumab every 3 weeks for 4 doses as assessed by PET.

The results from this biomarker study will be used to plan a randomized study so that investigators can further attempt to identify a subset of patients with HER2-positive breast cancer who do not require cytotoxic chemotherapy in addition to anti—HER2-targeted agents.

OncLive: Please discuss the advancements with neoadjuvant therapy in HER2-positive breast cancer.

In an interview with OncLive, Elizabeth A. Mittendorf, MD, PhD, an associate professor in the Department of Surgical Oncology at The University of Texas MD Anderson Cancer Center, discussed the evolving neoadjuvant treatment landscape and other developments in the field of HER2-postive breast cancer.Mittendorf: I would contend that most of us believe patients with HER2-positive breast cancer, particularly those who meet the criteria to receive pertuzumab in the neoadjuvant setting, would prefer that systemic therapy administered upfront.

As a surgeon, there are 2 reasons [for that]. The first is that it decreases the size of the breast tumor; therefore, a patient who required a mastectomy can now have a lumpectomy. An exciting area in breast surgical oncology is that we are also seeing some phenomena regarding the regional lymph nodes.

What advice do you have for community oncologists in the neoadjuvant space?

The FDA granted adjuvant pertuzumab priority review for patients with early-stage HER2-positive breast cancer. If this indication is approved, what impact could it have on the treatment landscape?

The other thing we are starting to embrace as a field is the idea of assessing response to therapy to dictate additional care. The pathology report after the patient receives their HER2-targeted therapy with chemotherapy in the neoadjuvant setting determines how the disease that is left will impact the decisions for other agents.The neoadjuvant approach has evolved our thinking about which patients to recommend. When the idea was first introduced, a lot of the rationale for giving the therapy upfront was to decrease the size of the tumor so that we can do a lumpectomy. We know from large trials that there is no difference in overall survival if we give chemotherapy in the neoadjuvant setting versus the adjuvant setting. Those trials are slightly dated since they look strictly at chemotherapy. Now, particularly in the HER2-positive space with these very specific HER2-targeted therapies, it gives us an opportunity to learn more about the individual patient's tumor biology, which can guide additional treatment.[This] is already a significant discussion within the breast oncology community, based on the results of the APHINITY trial that were presented at the 2017 ASCO Annual Meeting. It is an interesting situation where the trial met its endpoint and was statistically significant, but the conversation is determining if it is enough of a clinical benefit to warrant giving the therapy. I believe it is going to make the question of what to offer patients more challenging. It will be hard to determine which patient population needs this additional therapy.

How has the approval of neratinib affected the patient population?

APHINITY and pertuzumab, are getting a lot of attention; however, we also have to recognize that neratinib (Nerlynx) has also been recently FDA approved. The HER2 space has gotten more interesting. As a surgical oncologist, I am not prescribing this systemic therapy. In our practice at The University of Texas MD Anderson Cancer Center, we have not started using neratinib that often. One of the reasons is because it is a drug that is not easy for the patients. They can get a fair amount of diarrhea.

All groups are going to be challenged with developing their own algorithm or guidelines of who receives additional HER2-targeted therapy, which of the agents they are going to use, and the duration of treatment.