FDA Approves Enhertu for HER2-Positive Solid Tumors
Patients with advanced HER2-positive cancer now have a new treatment option. The FDA recently announced the expanded approval for Enhertu, making it the first tumor-agnostic HER2-directed therapy. Enhertu had previously been approved for unresectable or metastatic HER2-positive breast cancer and locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma.
Andreas Saltos, MD
“This is a significant approval, as it is one of only a few examples of pan-tumor drug approvals by the FDA in recent years. This is recognition that there are common biologies shared by a variety of cancers originating in different parts of the body and that appropriate ‘personalized’ therapies may be able to treat a variety of cancer types if there is a shared biological target,” said Andreas Saltos, MD, a medical oncologist in the Thoracic Oncology Department at Moffitt Cancer Center.
“This an important step forward. HER-2 overexpression varies according to the tumor, but it is around 2-3% of all solid tumors,” said Tiago Biachi, MD, PhD, a medical oncologist in the Gastrointestinal Oncology Department.
The new approval means Enhertu may be an option for patients with any cancer with HER2 overexpression, which means an excess of the HER2 protein on the cancer cell’s surface. It is typically tested using immunohistochemistry (IHC), a relatively simple test performed on tumor biopsy tissue.
“Currently, IHC testing is not routine practice for most cancers, so this approval could change that and make HER2 IHC testing more commonplace,” said Saltos, who was an investigator for one of the trials that led to Enhertu’s expanded approval.
“This is an important step in our field. It shows our need to test every patient and every tumor with a genomic panel. More than ever, we are treating cancer based on its gene features. Not simply guessing based on location or type. For example, we can’t simply say anymore, ‘You have gallbladder cancer, so take chemo’ unless we test first. Everyone needs to know there is an effective therapy available for the select cancers that are positive for HER2,” said Ben Creelan, MD, a medical oncologist in the Thoracic Oncology Department.
Enhertu is an antibody-drug conjugate, meaning an antibody is chemically linked to the drug. That antibody helps the medication, in this case, a type of chemotherapy, find and enter the tumor, where it kills cancer cells.
Monica Avila, MD
“This type of medication, an antibody-drug-conjugate, is a new way to get therapy into cells to reduce the risk of the systemic side effects typically seen when the drug is given directly. We are in the infancy of what these drugs can do, but the future is bright and full of new therapies,” said Monica Avila, MD, a medical oncologist in the Gynecologic Oncology Department.
The approval comes following several clinical trials testing Enhertu in patients with various cancer types. Results from the phase 2 trial DESTINY-PanTumor02, which included biliary tract, bladder, cervical, endometrial, ovarian and pancreatic patients with HER2 positive tumors, showed an overall response rate of 51% and a median duration of response of 19.4 months for those receiving the drug. Additional trials for HER2-positive colorectal and non-small cell lung cancers had similar findings.
