Breast Cancer : A Grand Slam – Dr. Nilesh D. Mehta

A Grand Slam in Breast cancer treatment – Dr. Nilesh D. Mehta

 

An estimated 290,560 new cases of breast cancer will be diagnosed in the United States in 2022. Of those patients who receive a diagnosis of the most aggressive form of the disease, metastatic breast cancer Stage IV, approximately 15-20% of such cancers will be considered HER2 positive and would be eligible to be treated with HER2-targeted therapies. The remaining 80% or so of metastatic breast cancers are currently categorized as HER2-negative, and of these cancers, approximately 55-60% express low levels of HER2. 

For breast cancer patients, treatment was directed at the HER2 overexpression on the cancer cells. Treatment with trastuzumab has been a game changer for several decades for a select group. This treatment with trastuzumab was primarily reserved for HER2 overexpression with 3+ on pathology testing. For HER-2 negative metastatic breast cancer patients, until now, anti-HER-2 therapy was not recommended. 

Dr. Shanu Modi and her colleagues embarked on a clinical trial which has received worldwide attention with tremendous hope and enthusiasm. DESTINY-Breast04 study is a clinical trial of historic proportions and a true game changer. It is essentially a grand slam to use baseball parlance. In this study,  patients received either standard chemotherapy of the physicians’ choice (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel), or trastuzumab deruxtecan, a new antibody-drug conjugate that links trastuzumab, a HER2 monoclonal antibody, to deruxtecan, a topoisomerase I inhibitor that interrupts DNA replication in cancer cells. Trastuzumab (Herceptin®) has been proven to be effective in cancers with high HER2 expression (called HER2-positive breast cancer) but not in cancers with low HER2 expression levels, hence trastuzumab has only been available for a subset of breast cancer patients. 

“Our study shows that trastuzumab deruxtecan may be a new and highly effective targeted therapy option available for this newly defined patient population,” said lead author Shanu Modi, MD, who is a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. “It is important for patients to know what level of HER2 their cancer expresses, not just whether it’s positive or negative, especially as HER2-low status can be determined using commonly available tests.”

“This trial’s findings show that trastuzumab deruxtecan doubles progression-free survival compared to chemotherapy alone in patients with HR+, HER2-low breast cancer. By effectively creating a new category of breast cancer, HER2-low, this trial will redefine how we classify breast cancer and will significantly expand the population of patients who can benefit from HER2-targeted therapy,” said Jane Lowe Meisel, MD, ASCO Expert in breast cancers.

 The use of trastuzumab deruxtecan (Enhertu®), a new HER2-targeting antibody-drug conjugate, doubled progression-free survival compared to standard-of-care treatment with conventional chemotherapy. It also significantly improved overall survival for patients with metastatic breast cancers expressing low levels of the HER2 receptor, regardless of hormone receptor status. These practice-changing findings identify a new subset of breast cancer – called HER2-low – and redefine how a large proportion of metastatic patients will be treated. A new disease category under breast cancer has been created which has a tremendous therapeutic opportunity for  metastatic breast cancer patients. What this means is that nearly 50% of metastatic breast cancer patients now have the potential to receive trastuzumab deruxtecan with a survival advantage. 

Trastuzumab deruxtecan is already approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received prior anti-HER2-based treatment. On April 27, 2022, the United States Food and Drug Administration granted Breakthrough Therapy Designation for trastuzumab deruxtecan in HER2-low metastatic breast cancer. The study was funded by Daiichi Sankyo, Inc., and AstraZeneca.

The results of the DESTINY-Breast04 study are huge and will help save the lives of thousands of women over the next few years.