"There have been many advances in the development of drugs for HER2-positive breast cancer since the introduction of Herceptin (trastuzumab) in 1998. The approval of Enhertu represents the newest treatment option for patients who have progressed on available HER2-directed therapies," 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. "Drug development in the area of targeted therapies builds on our scientific understanding of malignant diseases not only in breast cancer, but in multiple other diseases."
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.
The most common side effects for patients taking Enhertu were nausea, fatigue, vomiting, alopecia (hair loss), constipation, decreased appetite, anemia (hemoglobin in blood is below the reference range), decreased neutrophil count (white blood cells that help lead your body’s immune system response to fight infection), diarrhea, leukopenia (other white blood cells that help the immune system), cough and decreased platelet count (component of blood whose function is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot). Decreased neutrophil count is a potentially serious and common side effect as described in the Medication Guide. Patients treated with Enhertu may be at increased risk of developing left ventricular dysfunction, which occurs when the heart is unable to pump blood effectively to the body, as this has been seen with other HER2-directed therapies for breast cancer.
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.
The FDA granted the approval of Enhertu to Daiichi Sankyo.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.