Researchers and clinicians recently convened at the American Society of Clinical Oncology (ASCO), the world’s largest cancer conference, where the highly anticipated results of the DESTINY-Breast04 trial were announced.
DESTINY-Breast04 is a phase 3 trial that sought to determine if using [fam-] trastuzumab deruxtecan, an anti-HER2-antibody drug conjugate (ADC), was more effective than the standard-of-care treatment for patients with metastatic breast cancer and/or an unresectable breast cancer (a tumor that cannot be removed by surgery), that is HER2 low and who have been previously treated with one or two lines of chemotherapy.
Susan G. Komen’s Kimberly Sabelko, PhD., Vice President of Scientific Strategy and Programs, weighed in on why the DESTINY-Breast04 trial findings are important and what it means for patients.
Q: Let’s start with the basics. What is an antibody-drug conjugate?
Dr. Sabelko: Antibody-drug conjugates (or ADCs) are a fairly new, innovative class of anti-cancer drugs that link a targeted therapy (the antibody) with a chemotherapy into a single drug. They’re like guided missiles: the antibody portion of the ADC finds its target on the cancer cell surface, delivering the potent chemotherapy to kill the cancer cells.
The hope is that targeted delivery of chemotherapy drugs to the cancer cells will minimize damage to normal cells in the body and reduce systemic side effects. There is a lot of research being done to optimize the use of ADCs, like the one used in the DESTINY-Breast04 trial, to treat cancer.
Q: And what does HER2-low mean, and why is it important in this trial?
Dr. Sabelko: That is a great question, and a little background may help. HER2 (human epidermal growth factor receptor 2) is a protein that can be overexpressed on the surface of some breast cancer cells and is used as a fuel for them to grow. HER2 status is part of breast cancer staging and helps guide a patient’s treatment.
All breast cancers are tested for HER2 status, which is categorized as HER2-positive or HER2-negative. HER2-positive breast cancer cells have a lot of HER2 protein and can be treated with HER2-targeted therapies, such as trastuzumab (Herceptin). HER2-negative breast cancer cells have little or no HER2 protein. Trastuzumab and other FDA-approved, HER2-targeted therapies are not used to treat HER2-negative cancers.
“HER2-low” is a relatively new term used in research, including clinical trials like DESTINY-Breast04, to describe the subset of breast cancer cells that express low levels of HER2. Studies have shown that about 50% of breast cancers may be HER2-low.
Q: Tell us more about the DESTINY-Breast04 trial and why the findings are important.
Dr. Sabelko: The DESTINY-Breast04 trial found that patients with HER2-low unresectable and/or metastatic breast cancer benefitted from treatment with [fam-] trastuzumab deruxtecan. The findings are important because this is the first study where a HER2-targeted therapy offered clinical benefit for HER2-low metastatic breast cancers.
These results will likely be practice-changing in two ways: Right now, chemotherapy is the only treatment available for patients with endocrine-resistant, hormone receptor positive HER2-negative MBC and those with metastatic triple-negative breast cancer.The ability to target HER2-low tumors may offer a new, targeted treatment option for these patients. It may also change how HER2 status is reported and help guide treatment decisions for MBC.
Q: Is there anything else you’d like to share?
Dr. Sabelko: While the results of this study are exciting and may lead to new approaches to treat breast cancer, more research is needed to fully understand HER2-targeted ADCs, how they work, which patients will benefit from them and who may not. We will continue paying close attention to how this trial and others will transform patient care.
And lastly, I want to express my profound gratitude to the people who participated in this and so many other breast cancer clinical trials. Without them, no advances in breast cancer treatment would be possible!