On August 05, 2022, the U.S. FDA approved Enhertu (T-DXd) or (trastuzumab deruxtecan), an IV infusion to treat patients with unresectable (unable to be removed) or metastatic (progressed to other organs of the body) HER2-low breast cancer.
This is the first FDA-approved targeted therapy to patients with the HER2-low breast cancer subtype- a newly defined subset of HER2-negative breast cancer.
Richard Pazdur, M.D., director of the FDA’s OCE and acting director of the Office of Oncologic Diseases (OOD) in the FDA’s CDER said, “This approval highlights the FDA’s commitment to be at the forefront of scientific advances, making targeted cancer therapies available for more patients.”
“Having therapies that are specifically tailored to each patient’s cancer subtype is a priority to ensure access to safe and innovative treatments,” Richard Pazdur added.
Drug Overview: Enhertu (Fam-trastuzumab deruxtecan; AstraZeneca, Daiichi Sankyo) is a novel ADC or antibody-drug conjugate with 3 components: a humanized anti-HER2 immunoglobulin G1 monoclonal antibody with the same amino acid sequence as trastuzumab (Herceptin); a topoisomerase 1 inhibitor payload; and a tetrapeptide-based cleavable linker.
What is HER2-low Breast Cancer: HER2-low tumors are typically defined as those whose cells contain lower levels of a protein named HER2 on their surface. These tumors specifically account for around 50 to 60 percent of all breast cancers. A laboratory test known as immunohistochemistry is considered to find out whether HER2 exists at low levels in a tissue biopsy.
In HER2+ve breast cancer and in other cancers that overproduce HER2, too much HER2 on tumor cells drives cancer’s progression. Role of the protein named HER2 in HER2-low tumors is still not clear. Tumors with low levels of HER2 have traditionally been classified as HER2-ve because existing medicines that target HER2 were not useful in treating them. As a result, until now, HER2-low cancers have been treated as if they were HER2-ve.
DESTINY-Breast04: It is a randomized, multicenter, open-label clinical trial, in which a total of 557 adult patients with unresectable or metastatic HER2-low breast cancer were enrolled. This carried out trial included 2 cohorts: 494 HR+ patients and 63 HR- patients. Of these patients, 373 randomly treated with Enhertu by IV infusion every 3 weeks and 184 were randomly treated with a health specialist’s choice of chemotherapy (eribulin, gemcitabine, capecitabine, nab paclitaxel or paclitaxel). The outcomes demonstrated enhancement in both progression-free survival (PFS) and overall survival (OS) in individuals with unresectable or metastatic HER2-low breast cancer.
The median age of participants was 57 years, ranging from 28-81 years. Among the 557 patients, 24 percent were aged 65 or older. Females comprised 99.6 percent of the trial population. Participants’ race was reported as 48 percent White, 40 percent Asian, 2 percent Black or African American, and 3.8 percent Hispanic/Latino.
Reported Side Effects in DESTINY-Breast04: The most commonly reported side effects in patients with Enhertu in are fatigue, nausea, alopecia, vomiting, constipation, decreased appetite, diarrhea, and musculoskeletal pain. This medicinal product is not recommended for women who are pregnant.
Stats: It is estimated that 287,850 new cases of female breast cancer will be diagnosed in the year of 2022 in the U.S. Approximately 80 to 85 percent of those new cases were previously considered to be HER2-ve subtypes (including HR+ve and triple-negative breast cancer), which means the tumors do not overexpress or make excess copies of the HER2 protein. Of that proportion of breast cancer diagnoses, approximately 60 percent of patients previously classified as having HER2-ve subtype can now be considered as HER2-low. Prior to this approval, patients with HER2-low cancer received endocrine therapy or chemotherapy.