Dual HER2 Blockade in Early Breast Cancer

Stephanie Graff, MD, FACP: Anytime we have success stories in the metastatic setting like we’ve had with T-DM1 [trastuzumab emtansine] and pertuzumab, we very rapidly start thinking about moving those into the early stage setting to see if we can replicate those big gains in the curative-intent setting. Both pertuzumab and T-DM1 have moved into that space. Do you want to review the APHINITY trial?

Erika P. Hamilton, MD: Yes, absolutely. APHINITY studied therapy in the curative space. The trial looked at the addition of pertuzumab to trastuzumab compared to trastuzumab alone, obviously in combination with chemotherapy. What we saw was that pertuzumab added something, and particularly this looked like it was mostly in patients who were higher risk, as defined by patients who had lymph node-positive disease. There was an update recently about the 6-year data from pertuzumab, and this looked quite impressive—28% reduction in the risk of disease or death. And so, the absolute benefit was about 4.5%. With longer follow-up, we see this regardless of hormone receptor status. So this is whether patients are ER/PR [estrogen receptor/progesterone receptor]-positive or ER/PR-negative, as long as they express HER2. We did see fewer deaths on the arm receiving pertuzumab, but this has not reached statistical significance yet. So, it’s a little bit immature in follow-up.

Stephanie Graff, MD, FACP: I think that in the HER2-positive neoadjuvant and adjuvant spaces, we’ve seen this divergence where for the very early lymph node-negative, small lymph node-negative tumors—T1N0s—we are thinking more and more about how we can get away with less. In the lymph node-positive or larger tumors—T2N1 diseases—we are thinking about strategies to add on to try to continue to improve those already impressive survival outcomes, but continuing to try to move more and more patients into that curative setting.

I think that optimal patient selection has a huge role in the way that these studies are being designed. In APHINITY, it’s important to know that, again, like you alluded to, most of those patients were lymph node-positive or had T2 tumors. I think that represents how I’ve incorporated the use of neoadjuvant or adjuvant pertuzumab into my patient population.

Erika P. Hamilton, MD: Yes, absolutely. I won’t spoil anything. We’re going to talk about the KATHERINE [trial] a little bit later and how that may make us think about adjuvant pertuzumab a little bit differently. Certainly, I think this is very much the standard for our high-risk patients. Pertuzumab is available as the so-called TCHP regimen [docetaxel, carboplatin, trastuzumab, pertuzumab] in the neoadjuvant setting for anyone who has at least a 2-cm tumor or is lymph node-positive. I think you bring up a really good point. Sometimes finding the right words to express this idea of what we’re trying to get at is hard. We often use the terminology of escalating therapy or deescalating therapy, but that’s not quite right. It’s really about finding the right size treatment for the patient and their individual risk factors.

It’s a situation of riches right now in HER2-positive disease. We’re at the point now that if we get our hands on somebody in the early stage setting with HER2-positive disease, even if they’re lymph node-positive, upward of 90% of those patients are cured. So I think you’re right. It’s a time where we start thinking, are there some patients who we’re overtreating? And how can we pick that right size treatment for each patient to optimize their outcome, but also not give them more adverse effects than they need from the therapy?

Transcript edited for clarity.