Clinical Cases in HER2+ Breast Cancer - Episode 4

Case 1: Choosing Therapy for Early Stage HER2+ Breast Cancer 

Ruta Rao, MD: You brought up an excellent point about not forgetting about the toxicities that the nonanthracycline regimens contain. Are there any patients for whom you would not recommend neoadjuvant therapy? Dr Tolaney, you touched on your category of patients who fall into neoadjuvant therapy.

Sara Tolaney, MD, MPH: My preference has been to take patients to surgery up front if they have tumors that are under 2 cm and clinically node negative, with the idea being that these are clinically likely stage 1 HER2 [human epidermal growth factor receptor 2]–positive patients. We have some data to suggest that, in stage I patients, adjuvant therapy with paclitaxel and trastuzumab could be an option based on the APT [adjuvant paclitaxel-trastuzumab] data. We also have data from the ATEMPT trials suggesting T-DM1 [trastuzumab emtansine] is highly efficacious in these stage I, HER2-positive patients. For patients with clinically stage I disease, I generally take them to surgery up front, confirm that they have stage I disease, and then if so, I give them either adjuvant TH [taxane, trastuzumab] or T-DM1 [trastuzumab emtansine].

Ruta Rao, MD: Completing our discussion on neoadjuvant therapy for this patient, are there any other disease, clinical, or even patient-related factors that would come into play in making your decision about which therapy to give in neoadjuvant vs adjuvant? It’s always something we have to discuss with the patients, and oftentimes the patients come into us saying that they don’t understand why they have to have therapy before going to surgery. They just want the tumor removed. It’s part of our job to make them understand the importance of the neoadjuvant therapy in these cases.

Komal Jhaveri, MD, FACP: Absolutely.

Sara Tolaney, MD, MPH: That’s true. At first, it’s challenging for patients to think that you’re not taking them to surgery first. There is a natural reaction to want to get the tumor out and receive treatment afterwards. You’re right; that it is a real shift. It’s even been a shift for oncologists to move toward giving preoperative therapy. Knowing that we can better understand response to therapy and adapt based on achievement of pCR [pathological complete response] improves patients’ outcomes. It should be the standard of care to give preoperative therapy to stage II/III patients, and you’re right that it is something we need to continue to work on educating our patients about.

Komal Jhaveri, MD, FACP: Yes. The metanalyses where we’ve seen that pCR [pathologic complete response] rate in HER2-positive patients translate into better event-free survivals and overall survival help us support that decision. As you pointed out, Dr Rao, it’s important for us as physicians to highlight to our patients—at least for those patients who are questioning why are we not going for surgery first and getting the tumor out—that we are not only reducing the risk of distant occurrence, which is the goal of any chemotherapy systemically given, but also making an attempt to downstage the tumor both in the breast and the axilla. Understanding the response to therapy and, as Dr Tolaney pointed out, given the data, we now have to be able to adapt for patients who have residual disease and offer them adjuvant therapy based on that and improve their outcomes. It has become a compelling standard to offer these patients with stage II tumors and higher neoadjuvant therapies.

Ruta Rao, MD: Are there any clinical trials you might consider for this patient at your institutions?

Sara Tolaney, MD, MPH: Right now, our institution [the Dana-Farber Cancer Institute] has a trial that’s called the MARGOT trial. It is looking at a de-escalation strategy, and it is randomizing patients to receive THP [paclitaxel, trastuzumab, pertuzumab] weekly as paclitaxel with trastuzumab or pertuzumab or to receive paclitaxel with margetuximab and pertuzumab. It is looking to see if substituting margetuximab for trastuzumab in the preoperative setting could potentially lead to improvements in pCR. Of note, the trial is restricted to patients who have the CD16A-F allele, given some of the data we’ve seen from the SOPHIA trial, which we’ll discuss later on. We’ll have to see if that’s the case.

We will also soon be opening the COMPASS trial. This trial is looking at de-escalating therapy based on response to therapy. It is administering THP [paclitaxel, trastuzumab, pertuzumab] with either docetaxel or paclitaxel with trastuzumab and pertuzumab prior to surgery, and if a patient achieves pCR, that patient can go on to continue trastuzumab-pertuzumab. The idea being that this may spare patients more intensive chemotherapy and allow us to de-escalate now that we have dual HER2 therapy available. There are many other trials ongoing in this space, including 1 that’s even looking at an escalation strategy adding immunotherapy to preoperative treatment. We’ll see more options in the future, but it is nice to see that there are some de-escalation studies ongoing.

Komal Jhaveri, MD, FACP: For this particular patient, the COMPASS trial specifically would be an attractive option as well, especially if she achieved pathologic complete response to her up-front therapy with a THP [paclitaxel, trastuzumab, pertuzumab]–based approach if that’s what she began with. That way, we can offer her that therapy without having to escalate with additional systemic agents. If she had residual disease, the COMPASS study also allows a further randomization for patients with residual disease, so they could get either T-DM1 [trastuzumab emtansine] or T-DM1 [trastuzumab emtansine] with tucatinib. We can escalate where it’s needed and de-escalate for others. This is the way we’re trying to do right for our patients, so we can personalize their treatments and offer them the optimal therapy that a tumor can have good outcomes with.

Transcript edited for clarity.