A breast cancer drug from AstraZeneca and Daiichi Sankyo is now available FDA approval to address a brand new category of disease, a solution that allows targeted therapy to reach a much wider group of patients.
The drug, Enhertu, was originally approved to treat cancers characterized by an overabundance of a protein called HER2. The drug made headlines in June at the annual meeting of the American Society of Clinical Oncology, where Clinical trial investigators presented data showing that treatment with the drug also helped patients whose cancers had low levels of HER2— levels previously thought to be too low for therapies designed to target this protein. Instead of being classified as HER2 positive, such patients are classified as HER2 negative, making them ineligible for any targeted therapies. This is not a small group. Of the estimated 287,850 new cases of breast cancer in women that will be diagnosed in the U.S. this year, the FDA said 80 percent to 85 percent will be considered HER2 negative.
In approving Enhertu for so-called “low-HER2 cancers,” the FDA is defining a new subtype of breast cancer. Friday’s approval also makes AstraZeneca and Daiichi Sankyo’s drug the first targeted therapy for this new low-HER2 group. The decision was swift, coming less than two weeks after the companies announced that the FDA had accepted the application for the drug and will rate it under priority review. A regulatory decision was not expected for another four months.
“Today’s approval underscores the FDA’s commitment to being at the forefront of scientific advances, making targeted cancer treatment options available to more patients,” Richard Pazdur, director of the FDA’s Oncology Center of Excellence, said in a prepared statement. “Having therapies that are specifically tailored to each patient’s cancer subtype is a priority to ensure access to safe and innovative treatments.”
Enhertu is part of a class of cancer therapies called antibody drug conjugates (ADCs). These drugs are like smart bombs for cancer. They are produced by binding a targeting antibody to a useful tumor-killing drug. Enhertu combines the antibody trastuzumab with deruxtecan, a drug that damages cellular DNA to cause cell death. The targeting ability of the antibody is intended to protect healthy tissue from exposure to the toxic effects of the therapy.
The FDA’s new Enhertu decisoin is based on the results of an open-label phase 3 study involving 557 adults. These participants had advanced HER2-low breast cancer previously treated with chemotherapy. According to the results, the trial met its primary goal of showing an improvement in progression-free survival, which is how long patients live without the disease getting worse.
Although Enhertu’s targeted effect is designed to spare healthy tissue, ADCs still come with side effects. The most serious adverse effect reported in the clinical trial was interstitial lung disease, a condition that causes scarring and inflammation in the organ. The drug’s label carries a black box warning alerting clinicians to this risk. The label also indicates potential embryo toxicity; the drug is not recommended for pregnant women. The most common side effects reported in clinical trials include nausea, fatigue, hair loss, vomiting and constipation.
Shanu Modi, a medical oncologist at Memorial Sloan Kettering Cancer Center and the study’s lead investigator, told the ASCO meeting that for most patients, lung problems resulting from Enhertu are mild and reversible. She said the best way for clinicians to provide Enhertu is by selecting the patients best suited for therapy and monitoring for lung problems, then managing them if they occur.
Enhertus was originally developed by Daiichi Sankyo. This Japanese company started a partnership with AstraZeneca in 2019; later that year, the drug won accelerated approval to treat HER2-positive breast cancers that had not responded to at least two previous HER2-targeted therapies. Under the partnership, the two companies share in the development and commercialization of Enhertu worldwide, except in Japan, where Daiichi Sankyo holds the rights to the drug. Earlier this year, the FDA approved the drug’s use as earlier line of therapya solution that converts expedited approval to standard.
Public domain image from the National Cancer Institute