HER2 Low Breast Cancer: What Are the Latest Advancements in Novel Drug Antibody Conjugates for 2023? Yuan Yuan MD

HER2 Low Breast Cancer: What Are the Latest Advancements in Novel Drug Antibody Conjugates for 2023? Yuan Yuan MD

By Yuan Yuan, MD, PhD

There have been so many exciting things in our field, most recently including antibody drug conjugates specifically Trastuzumab Deruxtecan a monoclonal antibody in the HER2 low disease had largely changed our view of breast cancer. We used to put breast cancer into three bucket of triple-negative, HER2-positive, and ER positive. Now the HER2 low actually removed the old barrier and then put them into HER2 low was non HER2 low, so that’s very exciting. The data looks very promising. And also most recent FDA approval of Sacituzumab Govitecan in the HR positive, HER2 negative disease. Also adds additional options in the field of home receptor positive patient when they had had to move on to chemotherapy. They now have more options. I think the more challenge or future challenge would be how do we sequence the agents?

What were the questions you received from oncologists during your presentation on breast cancer treatment today?  

So one of the questions that got asked is, can we in hormone receptor positive HER2 negative. When they have to move on from endocrine treatment to chemo, is it now, are we ready to start Trastuzumab Deruxtecan or T-DXd instead of using single other single agent because the clinical trial was conducted in patients receive 1-2 lines of chemotherapy. So I think my answer for that question is that we’re not yet ready to move T-DXd to be the very first chemotherapy to be given. There is ongoing trials DESTINY-Breast06 clincal trial, is going to address that question. One of the questions I ask is, can we use oral selective estrogen receptor down regulator oral SERD Elacestrant in patient who doesn’t have ESR1 mutation? So I think that’s a also evolving question. The current FDA approval is tied into ESR1 mutation only patients, and there’s ongoing trial to test its efficacy. In the broader population because there’s a lot of calling, especially patients call my office, say, can we switch? I do not want that injection. The Fulvestrant is inject full form, which is some patients would favor oral. So I think the oral surge likely well become a very important players in the future treatment of ER positive disease.

What is the future for breast cancer research and treatments? 

So next step I think, will continue to leveraging genomic information to biomarkers to help us to tailor the therapy (Eg. targeted therapy), to personalize the treatment. And perhaps, in the early line setting, we made a comment earlier, for example, the neoadjuvant triple negative breast cancer therapy in the standard care now is KEYNOTE-522 based weekly Carbotaxel times 12, followed by AC times 4 on top of that adding Pembrolizumab. So in the sense we are somewhat, I would say escalating the treatment intensity, perhaps make the treatment longer. So how can we personalize the treatment (like targeted therapy)? Can we perhaps deescalate therapy for people who doesn’t need such so much therapy? So I think it also ties into ongoing ICE by 2.2 trials leveraging genomics imaging biomarkers to help us to predict who will hit complete pathological response. And those patients can go straight to surgery and those who doesn’t may continue to get more treatment. So I think we need to work on that, this is a calling from patients too.

Final Thoughts on Breast Cancer Research  

We’re making progress for sure. And we’re now having more arm momentum, so our job is to make sure we improve our patient’s understanding of those agents and perhaps. Do a better job monitoring toxicity, especially some of the toxicities not trivial from antibody drug conjugates from immunotherapy. There could be a delayed toxicity toward the future years. So I think we need to do a better job in monitoring these and then improve their quality of life.

What is HER2 Low Breast Cancer?

HER2 (Human Epidermal Growth Factor Receptor 2) is a protein that is present on the surface of some cells, including breast cells. When a breast cancer tumor has an overexpression of the HER2 protein, it is called HER2-positive breast cancer.

On the other hand, when a breast cancer tumor has a low level of HER2 protein expression or no expression at all, it is called HER2-negative breast cancer. Within the category of HER2-negative tumors, there is a subset of breast cancers that have very low levels of HER2 protein expression, and these are referred to as HER2 low. The classification of HER2 status is important because it can help guide treatment decisions, as HER2-positive breast cancer may respond differently to certain treatments than HER2-negative breast cancer.

10 Key Takeaways from Dr. Yuan Yuan’s MOASC Annual Meeting 2023 Presentation

1. Sacituzumab govitecan is an antibody-drug conjugate (ADC) that targets the Trop-2 protein, which is overexpressed in many solid tumors, including breast cancer.

2. The drug was granted accelerated FDA approval in 2020 for the treatment of patients with metastatic triple-negative breast cancer who have received at least two prior therapies.

3. Sacituzumab govitecan consists of an antibody that targets Trop-2 and a chemotherapy drug called SN-38, which is released when the antibody binds to Trop-2.

4. The drug has shown promising results in ongoing clinical trials, with response rates of up to 34% in patients with metastatic triple-negative breast cancer and hopefully lead to progression-free survival (PFS) and over all survival (OS) becoming statistically significant gathering data through statical analysis.

5. Patients who received sacituzumab govitecan also had longer progression-free survival (PFS) and overall survival (OS) compared to those who received standard chemotherapy.

6. The most common side effects of sacituzumab govitecan include nausea, diarrhea, decreased appetite, and fatigue, but these can be managed with supportive care.

7. The drug is currently being studied in other types of breast cancer, as well as other solid tumors, such as non-small cell lung cancer and urothelial cancer.

8. Ongoing research is focused on identifying biomarkers that can predict which patients will benefit most from sacituzumab govitecan.

9. Combination treatments, such as using sacituzumab govitecan with other drugs, are being explored to see if they can improve outcomes for breast cancer patients.

10. The development of sacituzumab govitecan represents an important advancement in the treatment of metastatic breast cancer, particularly for patients with triple-negative breast cancer who have limited treatment options and have disease progression.

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Yuan Yuan, MD, PhD – About The Author, Credentials, and Affiliations

CEDARS-SINAI APPOINTMENTS

• Director, Breast Medical Oncology
  Cedars-Sinai, Medicine

• Medical Director, Breast Oncology Disease Research Group
  Cedars-Sinai, Medicine

• Director, Breast Medical Oncology
  Cedars-Sinai, Cancer Institute

• Medical Director, Breast Oncology Disease Research Group
  Cedars-Sinai, Cancer Institute

DEGREES

• PhD
  University of California, Riverside, Riverside, United States

• Medical Degree
  Xuzhou Medical College, Xuzhou, China

CERTIFICATIONS

Medical Oncology
American Board of Internal Medicine, Philadelphia, United States