Neoadjuvant and Adjuvant Treatment Options for Patients With HER2-Positive Breast Cancer
Sara Hurvitz, MD, Fred Hutchinson Cancer Center, Seattle, Washington, shares insights on the neoadjuvant and adjuvant treatment options for patients with HER2-positive breast cancer. Dr Hurvitz discussed the different regimens in this setting and factors that may affect treatment decisions, as well as the possibility of trastuzumab deruxtecan in earlier settings.
Dr Hurvitz highlighted the importance of knowing a patient’s goals of care even in the curative setting, stating, “One cannot assume that a patient's goals are the same as the goals we would have for them based on efficacy.”
Transcript:
Sarah Hurvitz, professor of medicine, head of the Division of Hematology/Oncology at the University of Washington, Senior Vice President of the Clinical Research Division at the Fred Hutchinson Cancer Center.
Typically, when a patient is diagnosed with HER2-positive, non-metastatic breast cancer, we are offering, for the most part, neoadjuvant therapy, meaning treatment before surgery. This is because we know the response to neoadjuvant therapy at the time of surgery, pathologically speaking, is predictive of benefit from T-DM1 [trastuzumab emtansine] in the adjuvant setting.
If a patient has a tumor that is T1C or larger, that's HER2-positive, we will offer trastuzumab-based therapy with chemotherapy in the neoadjuvant setting. Most commonly the regimen used in the United States is the TCHP regimen, which is docetaxel, carboplatin, trastuzumab, and pertuzumab. Although there are studies looking at a lesser approach, for example, docetaxel, trastuzumab, and pertuzumab without the platinum agent.
At the time of surgery, patients who experience a pathologic complete response go on to receive maintenance HER2-targeted therapy with the addition of endocrine therapy if their tumor expresses the hormone receptor as well. Those patients with residual disease in the breast or lymph nodes will switch to trastuzumab emtansine in the adjuvant setting, which has been shown, based on the KATHERINE trial, to be associated with a significantly better invasive disease-free survival, as well as overall survival long-term.
And the question then becomes what do we do with patients who come in with very small, lymph node-negative, HER2-positive breast cancers? The NCCN guidelines recommend even for very small tumors, less than 5 mm, that we should be discussing HER2-targeted therapy and considering chemotherapy in these situations. Most of us are not utilizing neoadjuvant therapy for a tumor that's less than 1 cm. But it is something that can be discussed, for example, in a patient whose imaging shows very dense breast tissue and it's hard to estimate actual size of the tumor. I think before we make a decision regarding the use of neoadjuvant therapy versus going to surgery first, we should do a good imaging of the axilla to really understand: are the lymph nodes likely to be involved by cancer?
For those patients who go first to surgery and have stage 1 breast cancer, that's HER2-positive, we have the APT regimen, which is single-agent weekly paclitaxel for 12 weeks, with trastuzumab for a year. That regimen has been shown in a single-arm phase 2 study to be associated with really good long-term outcomes, out to 7 years, in excess of 90% disease-free survival, so, it's a very reasonable option. There are ongoing studies like the ATEMPT 2.0 study, which is looking at the use of T-DM1 instead of a standard chemotherapy, paclitaxel-based regimen in patients with stage 1 HER2-positive breast cancer. All of these studies are being done to sort of right-size and personalize therapy for patients diagnosed with early HER2-positive disease.
Is there potential for trastuxumab deruxtecan to move up from the metastatic setting?
Trastuzumab deruxtecan (T-DXd) has shown really remarkable efficacy in the metastatic setting for HER2-positive breast cancer. So, it's natural that it's now being looked at in early-stage disease that's high-risk for recurrence. There are studies ongoing looking at the use of trastuzumab deruxtecan in the neoadjuvant setting for HER2-positive breast cancer, and also studies looking at the use of trastuzumab deruxtecan in those patients who have residual disease at the time of surgery after standard neoadjuvant therapy. It's a KATHERLINE-like clinical trial that's being done to look at whether T-DXd is better than T-DM1 in those high-risk patients with residual disease after neoadjuvant therapy.
It may be that T-DXd moves up into the curative setting for patients with high-risk breast cancer. If that's the case and a patient who's had T-DXd in the neoadjuvant or adjuvant setting experiences a recurrence of their breast cancer that's metastatic, the question will become whether or not we reuse T-DXd in the metastatic setting, or what agents we can go on to give patients, and what will their efficacy be post–T-DXd. Every study that we do sort of begs new questions for our patients.
What are key considerations for clinicians treating patients in this population and setting?
I think it's key to always be aware of patient's comorbidities, as well as the other medications they're taking, as well as their goals of care. Goals of care is something we discuss a lot in the metastatic setting, but it also needs to be discussed and considered for patients who are being treated in the curative setting. One cannot assume that a patient's goals are the same as the goals we would have for them, based on efficacy. And as our agents do have life-threatening toxicities associated with them, as well as irreversible side effects that can come into play, it's really important for us to involve them in shared decision making.
