Enhertu (trastuzumab-deruxtecan) is an intravenous infusion treatment for low HER2 breast cancer that is unresectable (cannot be removed) or metastatic (spread to other parts of the body) and is the first therapy approved by the the US Food and Drug Administration (FDA) targeting patients with the HER2-low breast cancer subtype, which is a newly defined subset of HER2-negative breast cancer.
If a breast cancer is HER2 negative, the cancer cells do not contain high levels of the HER2 protein. HER2 receptors are proteins produced by the HER2 gene and must be considered when deciding on the best treatment for a patient. HER2-negative includes hormone receptor-positive and triple-negative breast cancers. HER2-low or low is a new classification of the HER2 subtype that constitutes a new subtype of breast cancer that has some HER2 proteins on the cell surface, but not enough to be classified as HER2 positive.
In Spain it is estimated that one in eight women will develop breast cancer throughout her life, since it is the most common type of cancer in women in our country, ahead of colorectal cancer, uterine cancer, lung or ovary, according to data from the GEICAM Breast Cancer Research Group. In the United States, 287,850 new cases of breast cancer are expected to be diagnosed in women this year.
“Having therapies specially designed for each patient’s cancer subtype is a priority to guarantee access to safe and innovative treatments”
Previously, about 80-85% of these new cases were considered to be of the HER2-negative subtype (including hormone receptor-positive and triple-negative breast cancer), which means that the tumors do not overexpress or make too many copies of the HER2 protein. Of that percentage of breast cancer diagnoses, approximately 60% of patients previously classified as HER2 negative subtype can now be considered HER2 low. Before Enhertu was approved, patients with low HER2 were given endocrine therapy or chemotherapy.
“Today’s approval highlights the FDA’s commitment to stay at the forefront of scientific advances, making specific cancer treatment options available to more patients,” said Richard Pazdur, MD, director of the Center for Excellence in Oncology. of the FDA and acting director of the Office of Oncological Diseases. at the FDA’s Center for Drug Evaluation and Research. “Having therapies specially designed for each patient’s cancer subtype is a priority to guarantee access to safe and innovative treatments.”
Efficacy and safety of Enhertu to treat low HER2 breast cancer
Enhertu, which has been developed by Daiichi Sankyo and AstraZeneca, is indicated for the treatment of those patients with low HER2 breast cancer who have received prior chemotherapy in the metastatic setting, or if their cancer has recurred during adjuvant chemotherapy or in the six months after the end of said treatment.
The drug’s approval is based on DESTINY-Breast04, an open-label, multicenter, randomized clinical trial involving 557 adult patients with unresectable or metastatic low HER2 breast cancer. Two cohorts were included in the study: 494 hormone receptor positive (HR+) patients and 63 hormone receptor negative (HR-) patients. Of these patients, 373 were randomly given Enhertu by intravenous infusion every three weeks, while 184 were randomly given their doctor-prescribed chemotherapy (eribulin, capecitabine, gemcitabine, nab paclitaxel, or paclitaxel).
The median age of trial participants was 57 years, with a range of 28 to 81 years. Among the 557 patients, 24% were 65 years of age or older and 99.6% of the total were women. 48% of trial participants were White, 40% Asian, 2% Black or African American, and 3.8% Hispanic/Latino. The trial results showed an improvement in both progression-free survival and overall survival in patients with unresectable or metastatic HER2-low breast cancer.
The most common adverse effects reported by participants receiving Enhertu in DESTINY-Breast04 are nausea, fatigue, hair loss, vomiting, constipation, lack of appetite, musculoskeletal pain, and diarrhea. The prescribing information includes a boxed warning to health professionals that warns of the risk of interstitial lung disease and embryo-foetal toxicity. Enhertu is not recommended for pregnant women.
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