Trastuzumab Deruxetecan

Trastuzumab deruxtecan is an antibody-drug conjugate used to treat certain cancers associated with human epidermal growth factor receptor 2 (HER2) expression or specific HER2 gene mutations. It combines trastuzumab, a humanized monoclonal antibody that targets HER2, with deruxtecan, a cytotoxic compound that inhibits topoisomerase I, an enzyme involved in DNA replication. After binding to HER2 on cancer cells, the medicine is taken into the cells, where the linker releases the cytotoxic component. This damages DNA and promotes cancer cell death. Its ability to deliver a potent anticancer agent to tumour cells makes it useful in selected cancers with different levels of HER2 expression, depending on the approved indication. Trastuzumab deruxtecan is administered by intravenous infusion under the supervision of an experienced oncology team. It is used as monotherapy in several settings and may be incorporated into combination or sequential treatment regimens where specifically approved. Its clinical applications include certain breast cancers, HER2-positive gastric or gastroesophageal junction adenocarcinoma, HER2-mutant non-small cell lung cancer, and selected other HER2-positive solid tumours. An important safety concern is interstitial lung disease or pneumonitis, which can occasionally be fatal. Appropriate patient selection, monitoring, and prompt assessment of respiratory symptoms are therefore essential during treatment.

Trastuzumab deruxtecan was developed through collaboration between Daiichi Sankyo and AstraZeneca as a targeted antibody-drug conjugate designed to deliver a topoisomerase I inhibitor to cancer cells expressing HER2. Its development has included major clinical trial programmes such as DESTINY-Breast, DESTINY-Gastric, DESTINY-Lung, and DESTINY-PanTumor studies. The United States Food and Drug Administration (FDA) first approved trastuzumab deruxtecan in December 2019 for a specified group of adults with previously treated, unresectable or metastatic HER2-positive breast cancer. Subsequent approvals expanded its use to additional breast cancer settings, gastric and gastroesophageal junction cancers, HER2-mutant non-small cell lung cancer, and certain other HER2-positive solid tumours. In May 2026, the FDA approved two additional indications in HER2-positive early-stage breast cancer: a neoadjuvant regimen followed by taxane, trastuzumab, and pertuzumab, and adjuvant treatment for eligible patients with residual invasive disease after specified neoadjuvant therapy. The European Commission authorised the medicine in the European Union in 2021, with subsequent extensions to its indications. The European Medicines Agency (EMA) provides the corresponding assessment and product information. Approval conditions, biomarker requirements, treatment lines, and available indications differ by jurisdiction. Indian use should be guided by the applicable Central Drugs Standard Control Organisation (CDSCO) authorisation and current prescribing information.

Trastuzumab deruxtecan is used for selected cancers according to tumour type, biomarker results, previous treatment, and local regulatory approval. In breast cancer, it is indicated in specified settings for HER2-positive disease, including selected early-stage disease and unresectable or metastatic disease. It is also used for eligible patients with HER2-low or HER2-ultralow metastatic breast cancer under particular conditions relating to hormone receptor status and prior treatment. In gastric or gastroesophageal junction adenocarcinoma, it is used for selected patients with HER2-positive advanced disease who have previously received trastuzumab-based treatment. In the United States, it is also approved for certain adults with unresectable or metastatic non-small cell lung cancer containing an activating HER2 mutation after prior systemic therapy, and for selected previously treated patients with HER2-positive solid tumours when no satisfactory alternative treatment options are available. Some approved early-stage breast cancer regimens use trastuzumab deruxtecan before surgery or after surgery, with treatment sequencing determined by the specific indication. It may be given alone or as part of a defined sequential regimen. HER2 status, disease stage, previous therapies, and the applicable national prescribing information should be reviewed before treatment is selected.

Trastuzumab deruxtecan is administered by intravenous infusion, generally once every three weeks, with the dose calculated according to body weight and the cancer indication. In many breast cancer and HER2-mutant lung cancer settings, the recommended dose is 5.4 mg/kg every three weeks. For certain gastric or gastroesophageal junction cancer settings, the recommended dose is 6.4 mg/kg every three weeks. Other approved regimens, including treatment for early-stage breast cancer, may involve a defined number of cycles or sequential therapy with other medicines. The initial infusion is generally administered over approximately 90 minutes; subsequent infusions may be given over approximately 30 minutes if the first infusion is tolerated, according to the product information. Treatment duration depends on the indication, disease response, recurrence risk, and tolerability. Therapy may continue until disease progression, unacceptable toxicity, or completion of the prescribed treatment course. Dose interruptions or reductions may be required for adverse effects such as interstitial lung disease, neutropenia, or other significant toxicities. Monitoring should include respiratory symptoms, blood counts, liver function, and cardiac function as clinically indicated. Treatment must be prescribed and supervised by an oncology specialist.

Common side effects of trastuzumab deruxtecan include nausea, vomiting, fatigue, reduced appetite, constipation, diarrhoea, hair loss, and changes in blood cell counts. Patients may develop anaemia, neutropenia, or thrombocytopenia, which can increase the risk of fatigue, infection, or bleeding. Other reported effects include elevated liver enzymes, headache, dizziness, and abdominal discomfort. Some patients experience reduced left ventricular function, so cardiac monitoring may be required, particularly in those with relevant risk factors or previous cardiotoxic treatment. Side effects vary according to the indication, dose, previous therapies, and whether other medicines are used as part of the treatment plan. Antiemetic medicines and other supportive measures may help manage nausea and related symptoms. Patients should report persistent symptoms, fever, unusual bruising, or worsening fatigue to their healthcare team. Although many adverse effects can be managed with medical support or treatment adjustments, new respiratory symptoms require particular attention because they may indicate interstitial lung disease or pneumonitis.

The most important warning associated with trastuzumab deruxtecan is interstitial lung disease (ILD) or pneumonitis, including cases that have been fatal. Symptoms may include a new or worsening cough, shortness of breath, fever, or difficulty breathing. Suspected ILD requires prompt clinical evaluation and appropriate investigation. Treatment should be interrupted while suspected cases are assessed and permanently discontinued for confirmed symptomatic ILD or pneumonitis of Grade 2 or higher, according to the applicable prescribing information. Other serious risks include neutropenia and other bone marrow toxicities, severe infection, left ventricular dysfunction, and infusion-related reactions. Severe nausea, vomiting, dehydration, or other gastrointestinal complications may also require medical intervention. Trastuzumab deruxtecan can cause embryo-fetal harm, so pregnancy status, effective contraception, and reproductive risks should be discussed before treatment. Patients should receive clear instructions on when to seek urgent medical care. Treatment may need to be withheld, dose-adjusted, or permanently discontinued depending on the severity and type of adverse event.

Before treatment, clinicians should confirm the relevant HER2 expression level or HER2 mutation using an appropriate validated test, depending on the indication. Baseline assessment generally includes a complete blood count, liver and kidney function tests, review of respiratory history, and evaluation of cardiac function when indicated. Existing lung disease, previous pneumonitis, prior chest radiotherapy, or previous treatments associated with pulmonary toxicity may require additional consideration. Patients with a history of cardiac disease or exposure to other cardiotoxic medicines may need closer cardiac monitoring. Pregnancy should be excluded before initiation where applicable, and patients should receive counselling about contraception and fertility-related concerns. Breastfeeding is generally not recommended during treatment and for the specified period after the final dose under the applicable product information. Trastuzumab deruxtecan is not associated with the same broad pattern of conventional metabolic drug interactions as many small-molecule medicines, but concomitant treatments can increase overlapping toxicities. Medicines that may cause lung injury, suppress bone marrow function, or affect cardiac function should be reviewed carefully. Vaccination plans, active infections, and other anticancer therapies should also be discussed with the treating team. Dose selection and monitoring should follow the current prescribing information for the specific indication.

Confirm the cancer indication, disease stage, HER2 test results or mutation status, and previous treatment history before dispensing or administering trastuzumab deruxtecan. Verify the indication-specific dose and schedule because the recommended dose differs between certain tumour types. Obtain baseline blood counts and liver function tests, assess respiratory symptoms, and arrange cardiac evaluation when clinically indicated. Counsel patients to report cough, breathlessness, fever, or any new respiratory symptoms immediately rather than waiting for the next appointment. Ensure that suspected interstitial lung disease is investigated promptly and that treatment is withheld or discontinued according to the severity of the confirmed event. Use appropriate antiemetic prophylaxis and monitor for neutropenia, anaemia, thrombocytopenia, and signs of infection. Infusions should be prepared and administered according to the product-specific handling instructions, with observation for infusion-related reactions. Review other medicines for overlapping pulmonary, cardiac, or bone marrow toxicity. Patients should also receive counselling on pregnancy prevention, breastfeeding restrictions, and when to seek urgent medical attention. Coordinated follow-up between oncology, pharmacy, nursing, and relevant specialist teams helps support safe treatment and timely management of adverse events.