Jan. 28, 2025 – The FDA has approved a new treatment for certain types of advanced breast cancer that have spread or cannot be removed with surgery.
Known as fam-trastuzumab deruxtecan but marketed under the brand name Enhertu, it is meant to treat advanced breast cancer that is HR-positive and HER2-low or ultralow, which has not improved after hormone therapy.
Breast cancer is the second most common cancer and a leading cause of cancer death among women in the United States. Each year, about 300,000 cases of breast cancer are diagnosed, with around 70% being HR-positive and HER2-negative. HER2 is a protein on the surface of breast cancer cells that promotes rapid growth and spread. While HER2-positive cancers respond well to targeted therapies, many HER2-negative tumors have low HER2 levels, and they're now recognized as HER2-low or HER2-ultralow cancers. Until recently, no targeted treatments were approved for these patients, and standard endocrine therapy followed by chemotherapy often showed limited effectiveness.
Enhertu belongs to a class of medicines called antibody-drug conjugates and is designed to target cancer cells while sparing the healthy ones. It combines a monoclonal antibody, trastuzumab, that targets HER2 with the chemotherapy drug deruxtecan. Enhertu gets selectively attached to HER2-positive cancer cells and releases the chemotherapy drug directly inside them, disrupting the cells’ DNA and stopping their growth. This allows for more precise and effective tumor targeting, even when HER2 expression is too low for other HER2-directed therapies to work. Enhertu was developed by AstraZeneca and Daiichi Sankyo and was first approved in December 2019.
The effectiveness of the drug was evaluated in a clinical trial involving 866 people with advanced HR-positive, HER2-low breast cancer whose cancer progressed after hormone or targeted therapies, without prior chemotherapy. Patients were randomly assigned to receive either Enhertu or standard chemotherapy. Results showed that Enhertu reduced the risk of cancer progression or death by 36%, compared to chemotherapy. Patients on Enhertu lived for 13.2 months on average without their cancer progressing, while those on chemotherapy lived for 8.1 months.
The most common side effects include low blood cell counts and hemoglobin and potassium levels, nausea, vomiting, constipation, diarrhea, reduced appetite, fatigue, hair loss, muscle or bone pain, and increased liver enzyme levels. In a news release, AstraZeneca explained that Enhertu can cause serious lung problems and advised patients to report any coughing, breathing issues, fever, or worsening symptoms to their doctor right away. Women of reproductive age should also tell their health care providers if they are pregnant or planning to get pregnant before starting Enhertu, as the medication can harm an unborn baby. Both men and women are also advised to talk to their doctors about using effective contraception during treatment and for four to seven months after the last dose.
