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FDA Approves Enhertu for HER2-Low Metastatic Breast Cancer


The Food and Drug Administration approved Enhertu for the treatment of unresectable or metastatic HER2-low breast cancer — marking the first targeted drug for this newly defined breast cancer subtype.

The Food and Drug Administration (FDA) on Friday approved Enhertu (fam-trastuzumab-deruxtecan-nxki) for the treatment of patients with unresectable or metastatic HER2-low breast cancer, marking the first targeted therapy approved for patients with HER2-low breast cancer.

"The approval of trastuzumab deruxtecan for HER2-low breast cancer, based on the dramatic results of the DESTINY-Breast04 trial, will have a significant positive impact for a large percentage of patients with metastatic breast cancer," Dr. Reshma Mahtani, chief of breast medical oncology at Baptist Health Miami Cancer Institute, said in an interview with CURE®.

The approval for the intravenous drug, which quickly follows the decision to grant Enhertu a priority review, is based off findings from the DESTINY-Breast04 clinical trial, which included 557 adults with unresectable or metastatic HER2-low breast cancer, of which 494 patients had HR-positive disease and 63 patients had HR-negative disease.

A total of 373 patients in the study were randomly assigned to receive Enhertu every three weeks, while 184 patients received physician’s choice of chemotherapy.

Patients who were given Enhertu tended to have better progression-free survival (time from treatment until disease gets worse) and overall survival (time from treatment until death of any cause) compared with those given chemotherapy.

According to findings presented at the 2022 American Society of Clinical Oncology Annual Meeting, average progression-free survival was 9.9 months for those given Enhertu, compared to 5.1 months for those given chemotherapy. Average overall survival was 23.4 months in the Enhertu group, compared to 16.8 months in the chemotherapy group.

The most common side effects seen for patients receiving Enhertu on the DESTINY-Breast04 trial were: nausea, fatigue, hair loss, vomiting, constipation, decreased appetite, musculoskeletal pain and diarrhea.

"The approval today of trastuzumab deruxtecan for patients with metastatic ‘HER2 low’ breast cancer represents a major advance in treatment options for our patients," Dr. Hope S. Rugo, director of breast oncology and clinical trials education at the University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, said in an interview with CURE®. "Not only do we have a highly effective therapy that improves survival, but the approval also helps to pave the way for studies in early stage disease. It is critical to scan the lungs every nine weeks for the first year and both hold drug and treat grade 1 asymptomatic ground glass opacities — and to be aware that late pneumonitis can occur. With careful monitoring and management, serious toxicity can be avoided."

Of note, the prescribing information for Enhertu included a boxed warning label advising about the risk of interstitial lung disease, which is inflammation in the lungs that can make it difficult for patients to get enough oxygen, as well as embryo-fetal toxicity. The FDA advises women who are pregnant not to take Enhertu.

HER2-low breast cancer is a newly identified subtype of the disease. According to the National Cancer Institute, there will be approximately 287,850 female breast cancers diagnosed this year; 80 to 85% of these cases would traditionally be labeled as HER2-negative, meaning that the tumors do not make an abundance of the HER2 protein.

However, experts estimate that approximately 60% of patients whose disease would typically be labeled HER2-negative actually have HER2-low breast cancer, meaning that there are some HER2 proteins on the surface of cancer cells, but not enough to be classified as HER2-positive.

"Today’s FDA approval of Enhertu for HER2-low advanced (metastatic) breast cancer is an important milestone in many ways," Dr. Debu Tripathy, chairman of the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, said in an interview with CURE®. "It represents one of the biggest 'leaps' compared to previously available therapies for this group of patients, representing nearly half of all advanced breast cancer cases.

"While many patients benefit significantly from other recent new drugs like cyclin-dependent kinase inhibitors, virtually all patients will develop resistance to therapy and exhibit progression of their disease," he continued. "Additionally, we are witnessing a dizzying pace of the development of new agents, the studies needed to prove they are effective and the regulatory process to approve the drugs and necessary diagnostic tests and to disseminate the knowledge among the patient care community and the public. We hope and expect this is a trend that will continue — our patients need the needle to move quickly and this is a day to remember that it can be done."

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