Trastuzumab deruxtecan

Trastuzumab deruxtecan (Enhertu or T-DXd) is an antibody-drug conjugate approved to treat HER2-positive or HER2-low breast cancer that cannot be removed surgically or that has spread to another part of the body (metastatic breast cancer).

T-DXd is given as the second treatment for people with metastatic breast cancer that has spread while on another drug therapy. T-DXd may also be the first treatment for a breast cancer that has returned within 6 months of finishing breast cancer treatment for early-stage disease.

T-DXd is the first medicine approved to target HER2-low breast cancer. HER2-low refers to breast cancers with an immunohistochemical (IHC) score of 1+ or 2+, less than the 3+ needed to be considered HER2-positive. To be eligible to receive this drug, a score of 2+ needs to be confirmed with a negative ISH test. While T-DXd is only FDA approved for metastatic breast cancer, it is being studied in clinical trials as a treatment for early-stage breast cancer.

How trastuzumab deruxtecan works

Trastuzumab deruxtecan is an antibody-drug conjugate. This type of treatment is a targeted therapy that combines two kinds of medicine: the anti-HER2 medicine trastuzumab and the chemotherapy deruxtecan. Trastuzumab directs the deruxtecan to the cancer cells, making it easier for the deruxtecan to reach and kill the cancer cells.

How antibody-drug conjugates work

In this video, Dr. Pallav Mehta, associate professor of medicine at MD Anderson Cancer Center at Cooper, explains in easy-to-understand language, how novel ADCs, such as trastuzumab deruxtecan (Enhertu), work to treat breast cancer.

Who gets trastuzumab deruxtecan

The Food and Drug Administration first approved trastuzumab deruxtecan (T-DXd) to treat metastatic, HER2-positive breast cancer that has grown after at least two past lines of HER2-targeted treatment for metastatic breast cancer. Since then, the approval has expanded based on the results of recent clinical trials. T-DXd can now be given as a:

• Second treatment for metastatic, HER2-postive cancer that has grown after treatment with another HER2-targeted therapy such as trastuzumab (Herceptin or biosimilar) or ado-trastuzumab emtansine (Kadcyla)
• Second treatment for metastatic, HER2-low breast cancer that has grown after treatment with chemotherapy
• First treatment for HER2-positive breast cancer or HER2-low breast cancer that has come back within 6 months of treatment for early-stage breast cancer

How trastuzumab deruxtecan is given

Trastuzumab deruxtecan is given by vein once every 3 weeks at your doctor’s office or infusion center. Your care team determines the dose by your weight, and you’ll receive it over about 30 minutes (90 minutes for your first infusion). Treatment can continue until the cancer grows or spreads to other parts of the body or you and your doctor decide to stop because of side effects.

Side effects & things to remember

In the clinical studies of trastuzumab deruxtecan, the people who took part reported these common side effects that you may experience:

• Nausea and vomiting
• Fatigue
• Low white blood cell counts
• Hair loss
• Constipation or diarrhea
• Low red blood cell counts

Men who take trastuzumab deruxtecan may experience fertility problems. If you plan to have children now or in the future, talk with your doctor before starting treatment.

In rare cases, some people developed a very serious lung condition called interstitial lung disease, or ILD. On scans, this disease looks like scarring or inflammation of the lungs. This condition can be fatal. In the clinical trial that led to the approval of T-DXd for HER2-low metastatic breast cancer, 12 percent of participants developed lung disease. Most had symptoms that were mild and treatable, but three participants (less than 1 percent in the study) died. If you have any lung problems while taking this medicine, it is very important to report them to your doctor immediately. These problems include:

• Cough
• Trouble breathing
• Shortness of breath
• Fever

Like other HER2-targeting medicines, trastuzumab deruxtecan can also affect your heart function. To monitor your heart, your doctor will recommend that you have an echocardiogram before starting treatment, and then every few months while you are on treatment.

While your doctor will watch for problems in your heart, let them know if you have symptoms such as sudden weight gain, swelling, or dizziness, or if you faint.

Trastuzumab deruxtecan may be dangerous to an unborn baby if taken during or before a pregnancy. You should not take it if you are pregnant or breastfeeding, and women of childbearing age should take steps to avoid getting pregnant while on trastuzumab deruxtecan. Men taking trastuzumab deruxtecan should also take steps to avoid getting a female partner pregnant.