Treatment Options for Patients With HER2-Positive Breast Cancer

Editor's Note: This video was recorded the summer of 2021.

Natasha Hunter, MD, Seattle Cancer Care Alliance, Seattle, Washington, discusses the different treatment options available for patients with HER2-positive breast cancer across the stages of disease. 

Transcript:

Hello, my name is Natasha Hunter. I am a clinical oncologist at Seattle Cancer Care Alliance and an assistant professor at the University of Washington in Seattle, and a cancer researcher there as well.

I've been asked to speak about my approach to HER2-positive breast cancer. I think as anyone who practices in this field knows, HER2-positive disease is a rapidly changing landscape, especially in the metastatic space. I also suspect that some of the new drugs that we've seen emerge in recent years may also find their way eventually into the early-stage setting, so it'll be interesting to see how that develops.

In terms of an approach, in early-stage HER2-positive breast cancer, the standard of care is fairly well established for small tumors less than 3 centimeters, node-negative, so, in other words, tumors that fall into the criteria established in the APT trial, the trial that was published in New England Journal of Medicine in, I believe, 2015, with Sara Tolaney [MD, MPH, Dana-Farber Cancer Institute]. If they fit into that criteria I usually favor upfront surgery and assuming that the pathology is consistent with that I go on, I think as most providers do, to provide or recommend 12 cycles of adjuvant Taxol [paclitaxel] and Herceptin [trastuzumab] followed by a year of trastuzumab therapy.

For larger and node-positive tumors, neoadjuvant therapy is the generally accepted approach, usually with TCHP [paclitaxel, carboplatin, trastuzumab, and pertuzumab] but dose-dense AC-THP [doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab] can be used, more widely in some institutions than others. It has fallen out of favor in lots of places given the potential for cardiac toxicity and, I think, perhaps to a lesser degree but still real, the concern for secondary malignancies. So with the anthracycline. Both regimens are effective. Obviously, you just need to be sure not to administer HER2-directed therapy in conjunction with the anthracycline and if I am giving dose-dense AC-THP, which I do on some occasions for various reasons, I always get a baseline echocardiogram prior to each therapy.

One area that I think varies according to clinical practice or individual practice, I think, is whether to continue Perjeta [pertuzumab] with the trastuzumab for a full year in cases where a pathological complete response is achieved after neoadjuvant therapy. I often do continue both agents if insurance permits, but I do maintain a low threshold to discontinue the pertuzumab for diarrhea primarily or other side effects. If there is residual disease after surgery I think I, along with most people, switch to [trastuzumab emtansine] T-DM1 per the KATHERINE trial to complete 17 cycles of T-DM1. And for these patients, if T-DM1 isn't tolerated, I do try to deescalate to trastuzumab-pertuzumab and not just trastuzumab.

Neratinib is available for patients after completion of therapy with trastuzumab to further protect against recurrence. It can be a hard medication to take, with diarrhea being the main limiting factor, and the benefit, at least to my mind, is fairly modest. I find that most patients are pretty tired after a year of therapy so I don't wind up giving it all that often, but it is an option and has been shown to have benefit for committed patients who want to maximally reduce risk. For all of these patients, obviously, if they're estrogen receptor-positive, I do start endocrine therapy as I initiate maintenance HER2-targeted therapy.

For metastatic disease the first line therapy is standardly THP [paclitaxel, trastuzumab, and pertuzumab], usually I find, for around 3 to 6 months depending on tolerance and if a really great response is achieved I withdraw the paclitaxel and continue on trastuzumab-pertuzumab maintenance. Some patients can have remarkably durable responses on this therapy alone. It can be an especially easy regimen now that Phesgo [pertuzumab, trastuzumab, and hyaluronidase] is available. Patients just come by the infusion center for an 8 or 10 minute injection and leave and most have pretty tolerable side effects and can lead a normal life.

The next line of therapy is usually T-DM1. I think that's still generally the case for patients without brain mets, although the FDA did approve tucatinib, capecitabine and trastuzumab for second-line therapy in 2020, although the associated trial, the HER2CLIMB trial, enrolled patients in the third-line. We still have lots of other chemotherapy, HER2-directed combinations, trastuzumab and lapatinib combined with capecitabine, gemcitabine, eribulin and so there's no standard ordering, but I think it is really encouraging to see how many options we have in this space and I'm really excited to see more and see how the field develops as we progress further in research.