Migrating Breast Cancer Cell
Credit: Christoph Burgstedt/Getty Images

On Friday, the U.S. Food and Drug Administration (FDA) approved trastuzumab-deruxtecan—sold under the brand name Enhertu—for the treatment of patients with unresectable or metastatic HER2-low breast cancer. Administered through IV infusion, the drug is the first approved therapy for patients with the newly identified HER2-low breast cancer subtype.

The expanded approval for Enhertu in the U.S., following its previous approval in second line HER2-positive metastatic breast cancer, allows for it to used across a spectrum of HER2-expressing breast cancer, including patients with HER2-low disease.

Of the more than 287,000 news cases of breast cancer diagnosed in the U.S. last year, between 80% and 85% were previously considered to be HER2-negative subtype. Of those cases, as many as 60% of patients previously classified as having HER2-negative subtype can now be considered as HER2-low.

“Today’s approval highlights the FDA’s commitment to be at the forefront of scientific advances, making targeted cancer treatment options available for more patients,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Having therapies that are specially tailored to each patient’s cancer subtype is a priority to ensure access to safe and innovative treatments.”

The approval came as a result of DESTINY-Breast04, a randomized, multicenter, open label clinical trial that enrolled 557 adult patients with unresectable or metastatic HER2-low breast cancer. The trial included two cohorts: 494 patients with hormone receptor positive (HR+_ breast cancer and 63 hormone receptor negative (HR-) patients. Of the total 373 randomly selected patients received Enhertu via intravenous infusion every three weeks while the remaining 184 patients in the trial randomly received a physician’s choice of chemotherapy—eribulin, capecitabine, gemcitabine, nab paclitaxel, or paclitaxel.

Results of the Phase III DESTINY-Breast04 trial were announced in early June at that American Society of Clinical Oncology Annul Meeting held in Chicago which showed a 49% reduction in the risk of disease progression or death versus chemotherapy in patients with HER2-low metastatic breast cancer with hormone receptor (HR)-positive disease. Subjects who received the drug also showed a 36% reduction in the risk of death, with a median overall survival of 23.9 months versus 17.5 months for those on chemotherapy.

The median age of trial participants was 57 years old, ranging from 28 to 81 years of age. Among the 557 patients, 24% were age 65 or older. Females comprised 99.6% of the trial population, with participants’ race comprising 48% White, 40% Asian, 2% Black or African American, and 3.8% Hispanic/Latino.

The drug, a specifically engineered HER2-directed antibody drug conjugate being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo, received a breakthrough designation from the FDA in April of this year, one of five such designations for Enhertu in indications ranging from breast cancers, to lung and gastric cancers. According to a press release, the approval comes roughly four months ahead of when it was anticipated.

“The rapid approval of Enhertu in HER2-low metastatic breast cancer by the FDA underscores the urgency to bring this transformational medicine to patients as quickly as possible. Patients with HER2-low tumors, who are identified through existing HER2 testing methods, will now have the opportunity to be treated based upon their HER2 status,” said Dave Fredrickson the EVP of the Oncology Business Unit at AstraZeneca.

The US regulatory submission for DESTINY-Breast04 was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, Enhertu is also under regulatory review for the same indication by the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada and Switzerland’s Swissmedic.

Regulatory applications for Enhertu are also currently under review in Europe, Japan and other countries based on the DESTINY-Breast04 results.

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