Breast cancer drugs from AstraZeneca and Daiichi Sankyo now available FDA Approved To address an entirely new class of disease, this decision enables targeted therapy to reach a wider patient population.
The drug, Enhertu, was originally approved to treat cancers characterized by the HER2-rich protein. The drug made a splash at the annual meeting of the American Society of Clinical Oncology in June, Treatment with the drug also helps patients with low levels of HER2 in cancer, data from clinical trial researchers show— levels previously thought to be too low for any therapy to target this protein. Instead of being classified as HER2 positive, these patients were classified as HER2 negative, making them ineligible for any targeted therapy. This is not a small group. Of the 287,850 new cases of breast cancer in women that will be diagnosed in the U.S. this year, 80% to 85% will be considered HER2 negative, the FDA said.
In approving Enhertu to treat so-called “HER2-low cancers,” the FDA is defining a new subtype of breast cancer. Friday’s approval also makes the drug from AstraZeneca and Daiichi Sankyo the first targeted therapy in this new HER2-low group.The decision was a quick one, after the two companies announced that the FDA had drug application accepted It will be assessed under priority review. No regulatory decision is expected for another four months.
“Today’s approval underscores the FDA’s commitment to staying at the forefront of scientific progress to bring targeted cancer treatment options to more patients,” Richard Pazdur, director of the FDA’s Oncology Center of Excellence, said in a prepared statement. “Targeting treatment for each patient’s cancer subtype is a top priority in ensuring 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 created by linking targeting antibodies to tumor-killing drug payloads. Enhertu linked the antibody trastuzumab to deruxtecan, a drug that damages cells’ DNA and causes cells to die. The targeting ability of the antibody is designed to protect healthy tissue from exposure to the toxic effects of the treatment.
The FDA’s new Enhertu decision is based on results from an open-label Phase 3 study that enrolled 557 adults. The participants had advanced HER2-low breast cancer and had previously received chemotherapy. Based on the results, the trial achieved its primary goal of showing an improvement in progression-free survival, or how long patients survive without disease progression.
Although Enhertu’s targeting is designed to protect healthy tissue, ADCs still have side effects. The most serious adverse reaction reported in clinical trials was interstitial lung disease, which causes scarring and inflammation of organs. The drug’s label carries a boxed warning alerting clinicians to this risk. The label also flags potential toxicity to the embryo; the drug is not recommended for pregnant women. The most common adverse reactions reported in clinical trials included nausea, fatigue, hair loss, vomiting and constipation.
Lung problems caused by Enhertu are low-grade and reversible for most patients, Shanu Modi, a medical oncologist at Memorial Sloan Kettering Cancer Center and the study’s principal investigator, told the ASCO meeting. The best way for clinicians to deliver Enhertu, she said, is to select the patients best suited for treatment and monitor lung problems, then manage them if they arise.
Enhertus was originally developed by Daiichi Sankyo. The Japanese company began its partnership with AstraZeneca in 2019; later that year, the drug received accelerated approval to treat HER2-positive breast cancer that has not responded to at least two early-stage HER2-targeted therapies. Under the partnership, the two companies share the development and commercialization of Enhertu globally, but Daiichi Sankyo owns the rights to the drug in Japan.Earlier this year, the FDA approved the drug as earlier line of treatmenta decision to convert accelerated approval to standard approval.
Public area picture by the National Cancer Institute
