A. Jo Chien, MD
Novel agents—including pertuzumab (Perjeta), neratinib (Nerlynx), and the investigational agent tucatinib—are rapidly expanding the armamentarium in HER2-positive breast cancer. The key now, explained A. Jo Chien, MD, is optimizing patient selection for these treatments.
“The challenge is finding the right spot for these agents and being able to show meaningful survival benefit,” said Chien. “The goal is maintaining quality of life equal to improving survival.”
In an interview during the 2018 OncLive®
State of the Science Summit™ on Breast Cancer, Chien, associate clinical professor, Department of Medicine, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, discussed emerging agents and other developments in HER2-positive breast cancer.
OncLive: What is being discussed in early-stage and metastatic HER2+ breast cancer?
: In the field of HER2-positive breast cancer right now, there are challenges in identifying patients who remain high risk despite trastuzumab.
There are a number of new agents, like pertuzumab and neratinib, that can be used in the early-stage setting. We know that despite trastuzumab, almost one-fourth of patients will relapse and require additional therapies.
On the flip side, there are patients who we are probably overtreating. Historically, our studies were done in patients with relatively high-risk disease—those with node-positive disease and larger tumors. Now, we are identifying patients with smaller tumors and node-negative disease and finding that maybe they don't need as intensive treatment.
Please expand on the emerging agents.
In the early-stage setting, that includes pertuzumab, which is an antibody against HER2 that blocks dimerization. We know that it improves pathologic complete response (pCR) rates in the neoadjuvant setting. We have also seen adjuvant data that have shown small benefit. The question is, “Who needs that additional benefit?” There are additional side effects that come along with it, such as diarrhea and rash.
Other agents include small molecule tyrosine kinase inhibitors, such as neratinib, which is also approved in the early-stage setting to be given for 1 year after completing 1 year of trastuzumab. The question is, as they’re both approved in the adjuvant setting, is, “Who needs both?”
What factors do you take into consideration when deciding on a therapy?
Pertuzumab is approved in both the neoadjuvant and in the adjuvant setting. We've seen from APHINITY that the benefit is about 1% to 2% in the overall population. However, in the higher-risk patients—those with node-positive and hormone receptor (HR)-negative tumors—the benefit is a little bit larger. Certainly, I would consider adding pertuzumab for those patients.
I don't know that recurrence is the only meaningful endpoint. We know that giving pertuzumab in the neoadjuvant setting can increase pCR, and therefore increase rates of breast conservation. This may minimize axillary surgery. How we manage the axilla is evolving as we're giving more neoadjuvant chemotherapy. Those are meaningful endpoints for patients, as well. Those who were taken to surgery first because they have small amounts of disease probably don't need adjuvant pertuzumab.
Similarly for neratinib, we're seeing the greatest benefit in patients who have higher-risk disease—node-positive with residual disease after neoadjuvant chemotherapy. [This is true] especially in those who have HR-positive disease. Those may be the patients to focus neratinib on.
What are your thoughts on de-escalation strategies?
For whom can we decrease the amount of chemotherapy? We started out with our most aggressive regimens, which include anthracyclines. Though the BCIRG-006 study was not powered to look at this, we saw very similar long-term outcomes out to 10 years between non-anthracycline and anthracycline-based chemotherapies. In the APT study in patients with stage I node-negative tumors, we saw great long-term outcomes with disease-free survival rates of 94% at 7 years of follow-up.
Also, who needs the full 1 year of trastuzumab? That was chosen arbitrarily. We know that patients do not benefit for longer than 1 year. We've seen data showing that less than 12 months can be equally beneficial. Those are the 2 current strategies with data.