How Trastuzumab Deruxtecan — Targets and Destroys Cancer Cells

HER2 is scored on a scale based on how much protein is present on cancer cell surfaces. A high score is called HER2-positive. A lower score that does not meet that threshold is now called HER2-low. Both HER2-positive and HER2-low breast cancer may be treated with trastuzumab deruxtecan, according to NCCN and ASCO guidance, though the exact indication depends on your cancer type, stage and prior treatment history. Your oncologist reviewed that result before recommending this drug for you.

It is both, in one molecule. The antibody component is a targeted therapy — it seeks out a specific protein on cancer cells. The payload component is a type of chemotherapy. Together they form a drug class called an antibody-drug conjugate. You may experience side effects associated with chemotherapy, such as nausea and hair thinning, because of the DXd payload. Your team will give you a full list of what to watch for before your first infusion.

Tumours are not uniform. Different cells within the same tumour can have different levels of HER2, and some areas may express less than others. If the drug only killed cells it directly entered, those lower-HER2 areas might be left behind. The bystander effect — where released DXd crosses into neighbouring cells — extends the reach of the treatment to cells the antibody did not directly enter. This is one reason trastuzumab deruxtecan shows activity in HER2-low cancers, not only HER2-positive ones.

Response is assessed through imaging — most commonly CT scans or PET-CT — at intervals your oncologist will specify. What is being looked for is whether tumours have reduced in size or metabolic activity, remained stable, or shown signs of growth. Tumour marker blood tests may also be used in some cancer types. You will not know from how you feel alone — the scan results are what guide the clinical decision about continuing treatment.

Yes, in a proportion of patients, cancer cells develop changes that reduce the drug's effectiveness — a process called acquired resistance. This is true of most cancer treatments, not only this drug. Research into why resistance develops and how to address it is ongoing. If your oncologist sees signs that treatment is no longer controlling the cancer, they will discuss the options at that point. Attending your scheduled scans is the most important thing you can do to ensure any change is caught early.

Interstitial lung disease — inflammation of the lung tissue — is the side effect your team will monitor most closely. It can range from mild, with no symptoms, to serious. Report any new or worsening shortness of breath, a dry cough, or fever to your team immediately — do not wait for your next scheduled appointment. Your team will also monitor for nausea, low blood cell counts, and other effects associated with the chemotherapy payload. You will receive a full list before your first infusion.