Advances in the Treatment of HER2+ Breast Cancer - Episode 5

Case 2: Overview of Treatment Strategies for HER2+ Metastatic BC

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Panelists provide a broad overview of treatment options available for patients diagnosed with HER2+ metastatic breast cancer.


Sara A. Hurvitz, MD: Now I would like to discuss a HER2-positive metastatic breast cancer case. This is a 57-year-old woman who was otherwise very healthy. She presented to her doctor after a 4-cm mass was found in her left breast on a routine mammography. A core biopsy demonstrated an ER/PR [estrogen receptor/progesterone receptor]-negative, HER2-overexpressing invasive ductal carcinoma. She had staging scans done, given the size and some symptoms that she was describing, that demonstrated 3 liver lesions up to 3 cm, as well as a solitary lung lesion. A liver biopsy was done, which confirmed metastatic breast cancer, de novo metastases. An MRI of the brain was done, which was negative for metastases. She received the THP [docetaxel, trastuzumab, pertuzumab] regimen for 6 cycles, followed by HP [trastuzumab, pertuzumab]. Of course, the THP regimen is supported by the CLEOPATRA clinical trial, which demonstrated, a decade ago now, that the addition of pertuzumab to TH [docetaxel, trastuzumab] improved not only the progression-free survival on the order of 6 months, but the overall survival as well, with a recent publication indicating the landmark overall survival at 8 years was 37%, which was 15% higher than the placebo arm. The median overall survival was almost 5 years. This regimen was tested in a patient population very similar to our patient; 90% of the patients on CLEOPATRA had never received trastuzumab. Many of the patients had de novo metastatic disease.

Some have called into question how applicable these results are in patients who have recurrent disease after treatment with TH, or even THP, in the adjuvant setting. With that said, this remains our standard of care therapy for patients as of 2022. This may be challenged in the next year or two with studies going head-to-head against this. This patient did receive it, and had a partial response in her breast mass and a complete response in the liver lesions. Eighteen months later while she was on maintenance HP, she had progression in her 3 liver lesions. The largest one went up to 1.5 cm after having completely resolved. She had new lesions that were growing. What I wanted to hear from you both is how you’re approaching the frontline setting, very briefly, in terms of choice between paclitaxel and docetaxel. What has your experience been in patients who’ve been pretreated in the adjuvant or neoadjuvant setting and have a recurrence? What is your timeline for using the THP regimen in terms of disease-free interval? Sara, could you deal with the first question, how do you choose the taxane, and what has your experience been with this regimen?

Sara M. Tolaney, MD, MPH: Generally speaking, this regimen is well tolerated. Our group typically will use paclitaxel instead of docetaxel. I find weekly paclitaxel is well tolerated by patients. The challenge is that you do have to come in weekly for the paclitaxel. Then we can give the HP potentially subcutaneously for people like every 3 weeks for IV [intravenous]. But I do like it, I find that patients tolerate it better than docetaxel, so generally, I’ll give that up front. Usually, we give it until we see maximal response, or until we see some adverse effects. People are starting to develop some neuropathy, for example, that’s another cue to me that we need to think about getting rid of the chemotherapy. Usually, that happens somewhere between 6 and 8 cycles, where people have had a really nice response to treatment, and we start to feel like they may be starting to develop some adverse effects from that. That’s when we’ll usually get rid of the chemotherapy and put them on what we call HP maintenance, just leaving them on the antibodies. This case was someone who had ER-negative disease. In that case, I too would’ve just left them on HP maintenance. However, if they had had ER-positive disease, I probably would’ve added an endocrine agent to that HP maintenance at that phase.

Sara A. Hurvitz, MD: Very good point. Bill, how are you selecting first-line therapy in a patient who has metastatic recurrence after adjuvant treatment? Is there a rough timeline you’re using where you’ll try a taxane, trastuzumab-based regimen, or pertuzumab if they’ve already seen that?

William J. Gradishar, MD: If they had adjuvant therapy and they had a long interval, I would still consider using THP as my first line; I don’t think that’s been displaced yet. But as noted, there are trials ongoing that may jeopardize its position as the first-line choice. Just a quick comment that we also tend to use docetaxel, but for patients who are coming from a distance, that’s the most attractive thing about it. For people who can make it in weekly, paclitaxel is better tolerated. I completely agree with what Sara [Tolaney] said. This is not common, but for patients who have a short interval between the completion of HP adjuvant therapy and the development of metastatic disease, it may give me pause about coming back with a regimen like THP as their first-line metastatic treatment. We might consider an alternative. Until recently, that would’ve been T-DM1 [trastuzumab emtansine], but I think trastuzumab deruxtecan becomes a choice that many of us would think about using.

Transcript edited for clarity.