FDA Approves Enhertu for Unresectable or Metastatic HER2-Low Breast Cancer
On Aug. 5, 2022, the U.S. Food and Drug Administration (FDA) approved the targeted therapy Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) to treat unresectable or metastatic HER2-low breast cancer that has been previously treated with chemotherapy:
for metastatic disease
after surgery for early-stage disease that came back (recurred) within six months of completing chemotherapy
Unresectable means the cancer can’t be removed with surgery.
Metastatic breast cancer is cancer that has spread to parts of the body away from the breast, such as the bones or liver.
About HER2-low breast cancer
Some breast cancer cells make, or overexpress, too many copies of the HER2 gene. The HER2 gene makes a protein known as a HER2 receptor. HER2 receptors are like ears, or antennae, on the surface of cells. These HER2 receptors receive signals that stimulate the cell to grow and multiply. But breast cancer cells with too many HER2 receptors can pick up too many growth signals and start growing and multiplying too much and too fast. Breast cancer cells that overexpress the HER2 gene are called HER2-positive.
Doctors use several tests to find out if a breast cancer is HER2-positive. Two of the most common are:
IHC (ImmunoHistoChemistry): The IHC test uses a chemical dye to stain the HER2 proteins. The IHC measures the amount of HER2 proteins on the surface of cells in a breast cancer tissue sample and gives it a score of 0 to 3+. If the score is 0 to 1+, it’s considered HER2-negative. If the score is 2+, it’s considered borderline. A score of 3+ is considered HER2-positive.
FISH (Fluorescence In Situ Hybridization): The FISH test uses special labels that attach to the HER2 proteins. The special labels have chemicals added to them so they change color and glow in the dark when they attach to the HER2 proteins. With the FISH test, you get a score of either positive or negative (some hospitals call a negative test result zero).
About 15% to 20% of breast cancers are HER2-positive. Still, research shows that more than 60% of breast cancers considered HER2-negative have some HER2 proteins on the surface of its cells. There just aren’t enough HER2 proteins for the cancer to be considered HER2-positive. Doctors now consider these cancers HER2-low.
There are medicines called targeted therapies that specifically target the HER2 receptors on HER2-positive breast cancer cells. Herceptin (chemical name: trastuzumab) was the first anti-HER2 medicine developed. Still, these anti-HER2 medicines have not been effective against HER2-low breast cancers.
Until now, HER2-low breast cancer was commonly treated as if it were HER2-negative breast cancer, almost always with chemotherapy.
Enhertu is a targeted therapy made up of three parts:
fam-trastuzumab: an anti-HER2 medicine that has the same basic structure as Herceptin (chemical name: trastuzumab)
a topoisomerase I inhibitor chemotherapy called DXd: topoisomerase I inhibitors work by interfering with a cancer cell’s ability to replicate
a compound that links the fam-trastuzumab molecule to the topoisomerase I inhibitor chemotherapy molecule
Doctors call Enhertu an antibody-drug conjugate targeted therapy. The combination of the topoisomerase I inhibitor and the linking compound is called deruxtecan. The linking compound attaches (conjugates) the fam-trastuzumab to the topoisomerase I inhibitor chemotherapy.
Enhertu is given intravenously, which means the medicine is delivered directly into your bloodstream through an IV or a port.
Enhertu also is approved by the FDA to treat unresectable or metastatic HER2-positive breast cancer in people who have previously received an anti-HER2 medicine:
for metastatic disease
before or after surgery for early-stage disease that came back (recurred) within six months of completing treatment
Research on Enhertu and HER2-low breast cancer
The FDA approval was based on results from the DESTINY-Breast04 study, which found that Enhertu improved both progression-free survival and overall survival in people diagnosed with previously treated metastatic HER2-low breast cancer when compared with doctors’ choice of chemotherapy.
Progression-free survival is how long a person lives without the cancer growing. Overall survival is how long a person lives, whether or not the cancer grows.
In the DESTINY-Breast04 study, the researchers defined breast cancer as HER2-low if it received an IHC score of 1+ or an IHC score of 2+ and a negative FISH test.
The FDA announcement included a definition of HER2-low breast cancer that seems to suggest the DESTINY-Breast04 study’s definition is to become the standard.
Enhertu side effects
In the DESTINY-Breast04 study, more than 99% of the people who received Enhertu and more than 98% of people who received their doctors’ choice of chemotherapy had at least one side effect. About a quarter of the people in each treatment group had a serious side effect.
About 16% of people who received Enhertu and about 8% of people who received their doctors’ choice of chemotherapy stopped the medicine because of side effects.
The most common side effects of any grade among people receiving Enhertu were:
nausea, experienced by 73% of the people
fatigue, experienced by 47.7% of the people
hair loss, experienced by 37.7% of the people
The most common grade 3 or higher side effects among people receiving Enhertu were:
low white blood cell count, experienced by 13.7% of the people
low red blood cell count, experienced by 8.1% of the people
fatigue, experienced by 7.5% of the people
What this means for you
If you’ve been diagnosed with metastatic breast cancer or early-stage breast cancer that can’t be removed with surgery, you may want to talk to your doctor about the HER2 test results in your pathology report. If the score was 1+ on an IHC test or a 2+ on an IHC test plus a negative FISH test, Enhertu may be an option for you.
Learn more about Enhertu.
Written by: Jamie DePolo, senior editor
— Last updated on August 11, 2022, 6:00 PM