The US Food and Drug Administration has approved the first targeted therapy for HER2-Low breast cancer

Today, the U.S. Food and Drug Administration has approved Enhertu (fam-trastuzumab-deruxtecan-nxki), an intravenous injection to treat patients with resectable (cannot be removed) or metastatic (spread to other parts of the body) HER2-low breast cancer. This is the first approved therapy targeting patients with the HER2-low breast cancer subtype, a newly identified subset of HER2-negative breast cancer.

It is estimated that 287,850 new cases of female breast cancer will be diagnosed in 2022 in the United States, and approximately 80-85% of those new cases were previously considered to be HER2 negative subtype (including hormone receptor positive and carcinomas). triple-negative breasts), which means the tumors do not overexpress, or make too many copies of the HER2 protein. Of this proportion of breast cancer diagnoses, about 60% of patients previously classified as having an HER2-negative subtype can be considered as HER2-low. Prior to today’s approval, HER2-low patients received either endocrine therapy or chemotherapy.

“Today’s approval highlights the FDA’s commitment to being at the forefront of scientific developments, making targeted cancer treatment options available to more patients,” said Richard Pazdur, director of the FDA’s Center of Excellence for Oncology and acting director of the Office of Oncology. At the Food and Drug Administration’s Center for Drug Evaluation and Research. “Having therapies tailored to each patient’s cancer subtype is a priority to ensure access to safe and innovative treatments.”

As part of the administration’s Cancer Moonshot Program, President Biden has hired federal agencies to develop ways to reduce cancer mortality, improve the lives of cancer patients and their families through advances in cancer research and technology, and develop new programs. Enhertu’s approval also demonstrates how FDA’s efforts align with Cancer Moonshot’s goals of targeting the right treatments to the right patients, accelerating progress against the most deadly and rare cancers, and learning from the experience of all patients.

HER2 receptors, which are proteins made by the HER2 gene, are important in determining a patient’s treatment. HER2-negative includes hormone receptor positive and triple negative breast cancer. HER2-low is a new classification of the HER2 subtype. It describes a new subtype of breast cancer that has some HER2 proteins on the cell surface, but it is not enough to classify it as HER2-positive.

Patients with low HER2 breast cancer are eligible for Enhertu if they have received previous chemotherapy in the metastatic setting, or the cancer has returned within, or within 6 months of completing adjuvant chemotherapy.

This approval is based on DESTINY-Breast04, a randomized, multicenter, open-label clinical trial of 557 adult patients with unresectable or metastatic low HER2 breast cancer. The trial included two groups: 494 hormone receptor-positive (HR+) patients and 63 hormone receptor-negative (HR-) patients. Of these patients, 373 patients were randomly assigned to receive Enhertu by intravenous infusion every three weeks and 184 were randomly assigned to a physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine, nab paclitaxel or paclitaxel). The results showed improvement in both progression-free survival and overall survival in people with unresectable or metastatic low HER2 breast cancer.

The average age of the trial participants was 57, ranging in age from 28 to 81. Of the 557 patients, 24% were 65 years of age or older. Females constituted 99.6% of the experiment population. The trial participants’ race was reported as 48% White, 40% Asian, 2% Black or African American, and 3.8% Hispanic/Latino.

The most common adverse reactions reported in patients receiving Enhertu in DESTINY-Breast04 are nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain and diarrhea. Prescribing information includes a boxed warning to advise healthcare professionals about the risks of interstitial lung disease and fetal toxicity. Enhertu is not recommended for pregnant women.

Enhertu has received priority review and advanced treatment assignments for this indication. The Food and Drug Administration (FDA) granted Enhertu approval to Daiichi Sankyo four months before the Prescription Drug User Fee Act (PDUFA) deadline.

This review was conducted under Project Orbis, an initiative of the Food and Drug Administration’s Center of Excellence for Oncology. The Orbis project provides a framework for the simultaneous submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Swiss Medica in Switzerland. Application reviews may be ongoing at other regulatory agencies.

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