U.S. Food and Drug Administration granted accelerated approval to Enhertu (fam-trastuzumab deruxtecan-nxki) for the treatment of adults with unresectable (unable to be removed with surgery) or metastatic (when cancer cells spread to other parts of the body) HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. Enhertu is a human epidermal growth factor receptor 2 (HER2)-directed antibody and topoisomerase inhibitor conjugate, meaning that the drug targets the changes in HER2 that help the cancer grow, divide and spread, and is linked to a topoisomerise inhibitor, which is a chemical compound that is toxic to cancer cells.
HER2-positive breast cancer is a type of breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. Approximately one of every five breast cancers have a gene mutation in the cancer cells that makes an excess of the HER2 protein. HER2-positive breast cancers are an aggressive type of breast cancer.
Enhertu’s approval was based on the results of a clinical trial enrolling 184 female patients with HER2-positive, unresectable and/or metastatic breast cancer who had received two or more prior anti-HER2 therapies in the metastatic setting. These patients were heavily pretreated in the metastatic setting, receiving between two and 17 therapies prior to receiving Enhertu. Patients in the clinical trial received Enhertu every three weeks and tumor imagining was obtained every six weeks. The overall response rate was 60.3%, which reflects the percentage of patients that had a certain amount of tumor shrinkage with a median duration of response of 14.8 months.
The prescribing information for Enhertu includes a Boxed Warning to advise health care professionals and patients about the risk of interstitial lung disease (a group of lung conditions that causes scarring of lung tissues) and embryo-fetal toxicity. Interstitial lung disease and pneumonitis (inflammation of lung tissue), including cases resulting in death, have been reported with Enhertu. Health care professionals should monitor for and promptly investigate signs and symptoms including cough, dyspnea (difficult or labored breathing), fever and other new or worsening respiratory symptoms. If these symptoms arise, Enhertu may need to be withheld, the dose reduced or permanently discontinued. Women who are pregnant should not take Enhertu because it may cause harm to a developing fetus or newborn baby, or cause delivery complications. The FDA advises health care professionals to tell females of reproductive age, and males with a female partner of reproductive potential, to use effective contraception during treatment with Enhertu.
Enhertu was granted Accelerated Approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need based on a result that is reasonably likely to predict a clinical benefit to patients. Further clinical trials may be required to verify and describe Enhertu’s clinical benefit.
The FDA granted this application Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition, when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Enhertu was also granted Fast Track designation, which expedites the review of drugs to treat serious conditions and fill an unmet medical need. This application was approved three months prior to the FDA goal date.
