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Dr. Carey Anders:
Welcome to The ASCO Post Roundtable Series on updates on HER2-Positive Breast Cancer. My name is Dr. Carey Anders, and I am the Medical Director of the Duke Center for Brain and Spine Metastasis, the Interim Division Chief for Medical Oncology, and also a practicing breast medical oncologist. I'm delighted to have my two colleagues here joining me today, Dr. Erica Hamilton and Dr. Sara Hurvitz, and I'll let them introduce themselves.
Dr. Erica Hamilton:
Hi, I'm Erica Hamilton. I am a breast medical oncologist. I direct the Breast Cancer Research Program at Sarah Cannon Research Institute in Tennessee Oncology in Nashville, Tennessee. Happy to join you two today.
Dr. Sara Hurvitz:
Hi there, I'm Sara Hurvitz from the David Geffen School of Medicine at UCLA Jonsson Comprehensive Cancer Center. I'm a medical oncologist and I direct the Breast Cancer Clinical Trials Program there.
Excellent. Thanks for joining. Today we'll be discussing recent updates in HER2-positive breast cancer and integrating these new developments into four patient case studies. Our third installment will focus on HER2-positive early-stage breast cancer, and some of the challenges in matching the patient's risk to their therapy to mitigate toxicities, but also maintain excellent clinical response.
Case study three is a 63-year-old female who was found to have a mammographically detected right-sided breast mass. Following her workup and a lumpectomy and sentinel lymph node biopsy, she was found to have a 1.2-centimeter T1C node-negative, highly ER/PR-positive, HER2-positive infiltrating ductal carcinoma. She presents postoperatively to your clinic to discuss systemic therapy options and wants to be as aggressive as possible. She's otherwise healthy. She works full time as an accountant and has two grandchildren that she enjoys spending time with. She meets with us in our clinic to discuss the next steps for therapy. I'll turn it over to Dr. Hamilton to sort of see how she would be thinking about this case and what the discussion with the patient would look like.
Yeah. I think that's a great case. This woman really has a node-negative, very small breast cancer. And although we know that HER2 cancers are more aggressive and are more likely to come back, these smaller cancers historically, I think we've been probably over treating some of these patients. We typically think about patients maybe needing some type of chemotherapy in combination with trastuzumab if the tumor size is over five millimeters, which this patient certainly is. But for this patient in her 60s with just right over about a one-centimeter tumor, I'd probably be thinking about adjuvant single-agent taxane with trastuzumab. The long-term results of that have really looked quite good.
Excellent. Dr. Hurvitz, from your perspective, I'm curious as to your approach and how you might address this case, if we change the tumor parameters a little bit. If, let's say instead of 1.2, the tumor's 2.1 centimeter and instead of ER/PR-positive, it's ER/PR-negative. What would be your thoughts there?
Yeah. Well, first of all, I would like to underscore that this situation is not that uncommon. There are some series that indicate stage I HER2-positive breast cancers are about 30% to 40% of HER2-positive breast cancers diagnosed, so it's not an uncommon problem to have a small node-negative tumor. But we know with HER2-positive disease, that size is not the issue. Even small tumors have a higher metastatic potential than similar size tumors that are HER2-negative. We have three fairly large series showing that. Biology seems to trump size and I do use HER2-directed therapy, even for tumors that are smaller than five millimeters, because I have seen the disease recur.
I completely concur with Dr. Hamilton, however, that probably we are vastly over-treating these small tumors with combination chemotherapy regimens. I think the Sara Tolaney APT (adjuvant, paclitaxel, and trastuzumab) regimen is a great one to be considered with very promising disease-free survival, even out to 7 years in excess of 90% for smaller tumors. And this study included patients who had tumors that were up to three centimeters. If this patient's tumor was 2.1 centimeters and ER/PR-negative, I still would discuss the APT regimen with her.
However, we know that the ER/PR-negative feature of a HER2-positive tumor does predict or is prognostic for a slightly worse outcome. In this patient who wants to be as aggressive as possible, I would also consider the TCH (docetaxel and carboplatin) regimen based on the BCIRG-006 study. This was based on a phase 3 randomized clinical trial showing benefits. So it truly is level one evidence, whereas the APT regimen was a single arm-phase II study. I think having that balance discussion with the patient, we do not have a head-to-head comparison of these two regimens in a patient like this. Probably one could argue TCH is overtreatment, but it is something that you could discuss if the patient is very motivated to be as aggressive as possible and the tumor is ER/PR-negative.
Perfect. And just to clarify, when you're speaking of the TCH regimen, you're speaking of the taxotere, carboplatin, and trastuzumab regimen, not the cyclophosphamide?
Correct. The docetaxel carboplatin trastuzumab regimen was studied in the BCIRG-006 Phase III Clinical Trial Against AC-TH and AC-T. The docetaxel cyclophosphamide trastuzumab regimen, again, is not based on a phase 3 clinical trial, but more of an exploratory phase 2 study showing good outcomes. But again, not that sort of level one evidence that the other TCH regimen has.
Right. No, absolutely. Thank you for clarifying. I really congratulate the APT study team for being so forward-thinking. This study now has 7-year follow-up and one of the kinds of glaring omissions in all of this conversation is anthracycline. I think that we've recognized over the years, the power of HER2-targeted antibody therapy. We know that the incorporation of an anthracycline does come with a small, but real risk of permanent cardiac dysfunction. So, I'm going to pull the team here to see if anyone would consider an anthracycline in this setting, and if so, why or why not?
No, I absolutely would not be thinking about anthracycline here. I'm hard pressed. It's very rarely for HER2-positive tumors that I do consider anthracycline. Now, we've had trials most recently trained, which was maybe designed a little bit differently than we give some chemotherapy here in the United States, but really doesn't look like now that we have dual HER2 therapy, that adding anthracycline adds a whole lot of efficacy. And it certainly, as you point out, does add additional risk. If we end up with cardiac dysfunction and patients can't complete their trastuzumab, etc., that really is much more costly for our patients.
I concur wholeheartedly. The only time I'm using an anthracycline for HER2-positive breast cancer is in a patient who is pregnant, where we know anthracycline have established safety during pregnancy, whereas taxanes and trastuzumab are contraindicated. So I think Erica's spot on. The TRAIN-2 regimen cemented it for many people, but if you add that to BCIRG-006, and TRYPHAENA, there are just so many studies now that have underscored the very similar outcomes with a non-anthracycline regimen. So, I think the NCCN (National Comprehensive Cancer Network) guidelines agree, they have removed anthracyclines from the preferred regimen.
Oh, beautiful discussion. Completely agree. I'm glad we're in this space now. So interestingly, this patient has an accountant background in finance. While she is not responsible for the cost of therapy, her insurance carrier is, she's quite surprised by the cost of antibody therapy. She asks about this in terms of, are there alternatives? And then also too, how can other entities absorb this cost? So I'm curious what you are learning about biosimilars in this space. If your institutions are using biosimilars and what data may be out there for similar efficacy.
We are definitely using biosimilars in our practice. In fact, it's insurance mandated. It's become kind of tricky and cumbersome from a logistical standpoint for us, because when we enter an order for trastuzumab, we have to wait and find out which biosimilar the insurance company will authorize. Then we have to reenter orders. These are very complex sort of decisions based on insurance authorization, but what's really important is that we talk to patients about the data relating to biosimilars and explain that these drugs have been shown to be similar to trastuzumab and that they are not getting a drug that's inferior in any way. It's really equivalent based on the studies that have been done and so I haven't had any pushback from patients. I think we've all embraced it in our oncology practice, and I do think that it helps keep the price of these expensive medications down.
I may just echo what Dr. Hurvitz said. We too are routinely using biosimilars. It's our go-to on our order set now for trastuzumab, I may also mention something that's a little bit similar. We now have some subcutaneous ways to administer trastuzumab and pertuzumab. It may not be as big of an issue in the United States, particularly for our patients that are receiving chemo and already have a port, etc., but it certainly can really extend therapy and make therapy possible in some other countries where having a port, IV treatments and a treatment chair, etc., can be a scarce commodity. So just as an awareness that those medications are out there as well and have increased uptake.
That is a fantastic point. I think both the use of biosimilars, which I would also say is exactly how things are moving forward at our center here just as you've described it yours, but then also the different formulations. The subcutaneous route may really increase access more globally.
A few key clinical takeaways from this case. I think de-escalation strategies, particularly for very early stage HER2-positive breast cancer have proven efficacious for really over a decade with follow up. I think we're all really glad to be able to balance and have the data in hand to balance the toxicities with the expected efficacy.
This approach will really help us decrease, minimize our side effects, particularly the longer-term side effects, as we've discussed the cardiac toxicity associated with anthracyclines, which really are very infrequently used in this setting. The financial toxicity is also a very important consideration. This comes into play not only here in the United States, but for global uptake of HER2-directed therapies, just as we've discussed. The use of biosimilars and alternative dosing strategies, such as subcutaneous, will really overcome this challenge for the future.
This brings us to the end of case three. Please, see the other segments for further discussion about the latest data in breast cancer, or you can also visit ASCOPost.com.