Erika P. Hamilton, MD
The treatment landscape for patients with HER2-positive breast cancer continues to evolve, with a potential new FDA approval on the horizon, explains Erika P. Hamilton, MD.
The FDA recently granted a priority review designation to a supplemental biologics license application for pertuzumab (Perjeta) for use in combination with trastuzumab (Herceptin) and chemotherapy for the adjuvant treatment of patients with HER2-positive early breast cancer.
With emerging options and established treatments, a challenge will be determining the correct sequence of systemic agents to give patients the maximum benefit with the least significant adverse events.
“The past several years have been exciting for HER2-positive breast cancer,” said Hamilton. “We had the approval of TDM-1 (ado-trastuzumab emtansine; Kadcyla), pertuzumab, neratinib (Nerlynx), and possibly more drugs over the next few years. For women who are going to be diagnosed with HER2-positive breast cancer and for those who have it now, it’s an exciting time for treatment.”
“A remaining challenge is that we have enough drugs, but we need to determine how to best sequence them. Whether we need to use them in combination or in sequence, it is important to determine the maximum benefit from them,” said Hamilton.
In an interview during the 2017 OncLive®
State of the Science SummitTM
on Breast Cancer, Hamilton, director of the Breast and Gynecologic Research Program at Sarah Cannon Research Institute, discussed the current treatment landscape for patients with HER2-positive breast cancer.
OncLive: Can you provide an overview of your presentation?
I provided updates in HER2-positive breast cancer, particularly in the early-stage setting, as well as the neoadjuvant and adjuvant data. We’ve recently received word that pertuzumab is on fast track for approval for consideration in early 2018 for adjuvant therapy.
I also discussed neratinib, which is a HER2-specific tyrosine kinase inhibitor (TKI) and the data in the adjuvant space after 1 year of trastuzumab. I [spoke on] some of the newer agents under investigation particularly for HER2-positive brain metastases, which is an area of unmet clinical need for women right now.
Can you further discuss the potential with neratinib?
Neratinib is an oral HER2-positive TKI. It is similar to lapatinib (Tykerb), it’s FDA approved, and it’s a pill that women take at home that blocks HER2. Specifically, the trial that resulted in neratinib’s approval (ExteNET) looked at neratinib versus placebo in women who had already completed their 1 year of adjuvant trastuzumab and they continued treatment for another year. Data showed that there was [about a] 2% improvement [with neratinib versus placebo] in women who did not see their cancer come back during that time frame.
What is the role of extended adjuvant therapy?
The role of extended adjuvant therapy in HER2 may not be quite as clear cut as estrogen receptor–positive disease, but there is a benefit. For those women who have a higher risk and are motivated, it is a reasonable option.
It is important to be careful with neratinib due to the toxicity, as there is significant diarrhea [associated] with this drug. For women who are having trouble tolerating it despite antidiarrheals, or for women who do not have a high risk for recurrence, it may not be worth it in this setting. However, for women who are high risk and can tolerate it, it is a valuable option.
What are some of the newer agents for patients with brain metastases?
One of the newer agents is a drug called tucatinib, previously known as ONT-380. It is a TKI but, as opposed to neratinib and lapatinib, it only blocks HER2 and does not block HER1 or EGFR. The side effects of neratinib and lapatinib, such as rash and diarrhea, come from blocking HER1.