Trastuzumab deruxtecan

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

T-DXd is the first medicine approved to treat breast cancers that are HER2-positive, HER2-low, or HER2-ultralow. Until recently, only HER2-positive breast cancers were treated with HER2-targeted medicines. HER2-low and HER2-ultralow were considered HER2-negative. These are new definitions, and doctors are still slowly adopting them into their regular care. 

• HER2-positive breast cancer means there is a high amount of HER2 protein on the surface of the cancer cells. To be HER2-positive, the breast cancer must have an immunohistochemistry (IHC) test score of 3+, or a positive result on an in situ hybridization (ISH) test. The most commonly used ISH test is called a FISH test. 
• HER2-low breast cancer has a smaller amount of HER2 protein. This means an IHC score of 1+ or 2+ with a negative ISH test. 
• HER2-ultralow breast cancer has an IHC score of 0 but shows very small amounts of HER2 on the cell surface. In these cases, more than 0% and up to 10% of cancer cells show very low levels of HER2, sometimes called “faint or incomplete,” and ISH testing is negative. 

T-DXd is FDA approved to be given:  

• In combination with pertuzumab (Perjeta) as a first treatment for people with HER2-positive metastatic breast cancer 
• Alone as a treatment for people with HER2-positive metastatic breast cancer or breast cancer that can’t be removed with surgery (unresectable); this requires previous treatment with anti-HER2 medicines, either for metastatic breast cancer or for early-stage breast cancer that has recurred within 6 months of finishing early-stage treatment
• Alone as a treatment for people with metastatic or unresectable HER2-low breast cancer who have been treated with chemotherapy, or breast cancer that has come back within 6 months of finishing chemotherapy for early-stage disease 
• Alone as a treatment for people with metastatic or unresectable hormone receptor-positive, HER2-low, or HER2-ultralow breast cancer that has grown after taking hormonal therapy 

While T-DXd is only FDA approved for metastatic breast cancer or breast cancer that cannot be removed surgically, 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 while trying to limit the effect on normal cells.

Who gets trastuzumab deruxtecan

The U.S. Food and Drug Administration first approved trastuzumab deruxtecan (Enhertu, sometimes called T-DXd) on December 20, 2019 for people with HER2-positive metastatic or unresectable breast cancer that was already treated with at least two HER2-targeted therapies.  

Since then, new approvals have expanded its use in breast cancer. T-DXd is now approved to treat: 

• HER2-positive metastatic breast cancer, in combination with pertuzumab (Perjeta) as a first treatment  
• HER2-positive breast cancer that has come back (recurred) during or within 6 months of finishing early-stage HER2-targeted treatment 
• Metastatic HER2-low breast cancer after previous chemotherapy, or breast cancer in people who had a recurrence within 6 months of completing chemotherapy for early-stage breast cancer 
• Hormone receptor-positive, HER2-low, or HER2-ultralow metastatic breast cancers that have grown after one or more hormonal therapies 

T-DXd is still being studied in early-stage HER2-positive disease. 

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
• Inflammation of the lungs (rare)
• Lower pumping function of the heart (rare)

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% of participants developed lung disease. Most had symptoms that were mild and treatable, but three participants (less than 1% 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.