Trastuzumab deruxtecan is a targeted therapy used to treat specific types of cancer. Known by its brand name, Enhertu, this medication is part of a class of drugs called antibody-drug conjugates, or ADCs. An ADC is a complex medication designed to deliver a cell-killing agent directly to cancer cells. This treatment was first approved by the U.S. Food and Drug Administration (FDA) in 2019.
How Trastuzumab Deruxtecan Works
Trastuzumab deruxtecan functions as a highly specialized delivery system, combining two distinct components to attack cancer cells. The first part is trastuzumab, a man-made protein known as a monoclonal antibody. This antibody acts as a guidance system, seeking out and binding to a specific protein on the surface of some cancer cells called human epidermal growth factor receptor 2, or HER2. When cancer cells have an abnormally high amount of HER2, it helps them grow and divide uncontrollably.
Once the trastuzumab antibody attaches to the HER2 protein on a cancer cell, the entire drug complex is pulled inside the cell. This process allows the second component, deruxtecan, to be released. Deruxtecan is a chemotherapy drug, categorized as a topoisomerase I inhibitor. After being released inside the cancer cell, it works by causing DNA damage, which leads to the cell’s death.
By using the antibody to home in on HER2-expressing cells, the chemotherapy payload is delivered more directly to the cancerous tissue. This mechanism is also believed to have a “bystander effect.” This is where the deruxtecan released from a target cell can pass through the cell membrane and kill nearby cancer cells, even if they have lower levels of HER2.
Cancers Treated With This Medication
This medication is approved for several types of cancer that are characterized by the presence of the HER2 protein. One primary use is for treating HER2-positive breast cancer that is unresectable, meaning it cannot be removed with surgery, or has spread to other parts of the body. It is used in patients who have already received one or more prior anti-HER2 treatments.
The application of trastuzumab deruxtecan has expanded to include a newer classification known as HER2-low breast cancer. These are breast cancers that have some HER2 proteins on their surface but not enough to be classified as HER2-positive. This development provides a treatment avenue for a larger group of patients with metastatic breast cancer who previously had fewer targeted options available after chemotherapy.
Beyond breast cancer, this drug is also used for other HER2-related malignancies. It is approved for adults with HER2-positive gastric (stomach) or gastroesophageal junction adenocarcinoma that has advanced or spread, particularly after a previous trastuzumab-based treatment has been tried. Another approved use is for non-small cell lung cancer (NSCLC) in patients whose tumors have a specific type of HER2 mutation and who have received prior systemic therapy.
The Administration and Treatment Cycle
Trastuzumab deruxtecan is administered as an intravenous (IV) infusion within a hospital or clinical setting. The treatment is given on a recurring schedule, once every three weeks, which constitutes one treatment cycle. This cycle is repeated unless the disease progresses or the patient experiences unacceptable side effects.
The infusion process is carefully managed by a healthcare team. The first dose is administered slowly, usually over 90 minutes, to monitor for any immediate infusion-related reactions. If the initial treatment is well-tolerated, subsequent infusions can be completed more quickly, typically over 30 minutes.
Before the infusion begins, patients are given pre-medications. These can include drugs to prevent nausea and vomiting, as trastuzumab deruxtecan is known to cause these side effects.
Potential Side Effects and Management
Patients receiving trastuzumab deruxtecan may experience a range of side effects. Among the most common are:
- Nausea
- Fatigue
- Vomiting
- Hair loss
- Constipation
- Decreased appetite
The treatment can also affect blood cell counts, leading to lower levels of white blood cells, red blood cells, and platelets. Medical teams regularly perform blood tests to monitor these counts and may adjust treatment if they become too low.
A serious risk associated with this medication has prompted a black box warning from the FDA. This warning highlights the potential for severe or life-threatening interstitial lung disease (ILD) or pneumonitis, which involves inflammation and scarring of the lungs. Patients are instructed to immediately report any new or worsening respiratory symptoms to their doctor, such as coughing, trouble breathing, or fever. If ILD is suspected, treatment is interrupted, and corticosteroids may be administered.
Another serious, though less common, side effect involves heart function. The drug can cause a decrease in the heart’s ability to pump blood effectively, known as left ventricular dysfunction. A patient’s heart function may be assessed before and during the treatment course. Management of side effects is a continuous process, and doctors may pause treatment, reduce the dose, or discontinue the drug altogether depending on the severity of the reaction.