Trastuzumab

Trastuzumab is a humanised monoclonal antibody and targeted anticancer medicine used for certain cancers that overexpress human epidermal growth factor receptor 2 (HER2). HER2 is a protein involved in cell growth and survival; in some breast and stomach cancers, excessive HER2 activity can contribute to tumour development and progression. Trastuzumab binds to the HER2 receptor on cancer cells, interfering with growth signalling and helping the immune system recognise and destroy targeted cells. It is administered intravenously, while certain specifically approved formulations are given by subcutaneous injection. Treatment is considered only when appropriate tumour testing confirms HER2 positivity according to the relevant product's prescribing criteria. Trastuzumab may be used alone in selected settings or combined with chemotherapy, hormonal therapy, or other anticancer treatments, depending on the cancer type and stage. It has an established role in both early-stage and metastatic HER2-positive breast cancer and in selected HER2-positive metastatic gastric or gastroesophageal junction cancers. Because treatment can affect heart function and may cause infusion reactions or lung complications, patients require appropriate assessment and monitoring before and during therapy. The treatment plan depends on the indication, formulation, previous treatment, and individual clinical circumstances.

Trastuzumab was developed as a targeted antibody against HER2 after research identified the receptor as an important therapeutic target in a subset of cancers. Clinical trials established its role in HER2-positive breast cancer and later supported use in selected gastric and gastroesophageal junction cancers. The United States Food and Drug Administration (FDA) first approved trastuzumab in September 1998 for HER2-positive metastatic breast cancer; its approved indications were subsequently expanded. The European Commission granted marketing authorisation for Herceptin in the European Union on 28 August 2000. Later clinical programmes evaluated trastuzumab in early breast cancer, metastatic disease, and combination regimens. Regulatory approvals depend on the specific formulation and indication, and biosimilar trastuzumab products may have their own authorised prescribing information. In India, the Central Drugs Standard Control Organisation (CDSCO) governs relevant product approvals. The approved indications and formulations available locally should be confirmed before treatment.

Trastuzumab is used for cancers that meet the relevant HER2-positive testing criteria. In breast cancer, it may be used for early-stage disease as part of treatment before or after surgery, often in combination with chemotherapy, and for metastatic disease either alone in selected circumstances or with other anticancer medicines. Depending on the indication, combination partners may include taxanes or other chemotherapy agents, and selected postmenopausal patients with hormone receptor-positive metastatic disease may receive it alongside hormonal therapy. Intravenous trastuzumab is also approved for selected patients with HER2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction, generally in combination with chemotherapy. Treatment eligibility depends on tumour type, stage, prior therapy, HER2 test results, and the applicable local prescribing information. Trastuzumab should not be assumed to be suitable for every cancer or every tumour that expresses HER2 at low levels.

Trastuzumab is administered intravenously, while certain authorised formulations are administered by subcutaneous injection. For common intravenous regimens in breast cancer, a three-weekly schedule uses an initial loading dose of 8 mg/kg followed by 6 mg/kg every three weeks; an alternative weekly schedule uses a 4 mg/kg loading dose followed by 2 mg/kg weekly. The appropriate regimen depends on the indication and treatment plan. Subcutaneous formulations have different dosing instructions and must not be substituted dose-for-dose without following their specific product information. In early breast cancer, treatment is commonly planned for a total duration of about one year, subject to recurrence and tolerability; in metastatic disease, treatment may continue while it remains effective and tolerable. Infusions must be administered by trained healthcare professionals, with observation for reactions during and after administration. Cardiac function should be assessed before treatment and monitored during therapy. Exact dosing, interruptions, and treatment duration must follow the approved regimen for the individual patient.

Common side effects of trastuzumab may include fever, chills, headache, nausea, diarrhoea, fatigue, and infusion-related symptoms. Some patients experience reactions during or shortly after administration, particularly with early infusions. When trastuzumab is combined with chemotherapy, additional effects such as hair loss, reduced blood cell counts, or nausea may occur depending on the other medicines used. The frequency and severity of side effects vary between patients and treatment regimens. Healthcare professionals may manage symptoms with observation, supportive treatment, or adjustments to the treatment schedule. Patients should report new or persistent symptoms and should not change or stop treatment without discussing it with their treating team.

Important risks include cardiomyopathy, reduced left ventricular ejection fraction, and congestive heart failure. The risk of cardiac complications may be higher when trastuzumab is used with anthracycline chemotherapy or in patients with pre-existing heart disease. Serious infusion reactions, anaphylaxis, and pulmonary toxicity, including interstitial pneumonitis or acute respiratory distress syndrome, can occur. Exposure during pregnancy may cause harm to the developing fetus, including low amniotic fluid and related complications; pregnancy status, reproductive plans, and effective contraception should therefore be discussed before treatment. Trastuzumab may need to be withheld or discontinued for significant cardiac dysfunction, severe infusion reactions, or serious pulmonary complications, according to prescribing guidance. Patients should promptly report breathlessness, new swelling, persistent cough, chest discomfort, or symptoms suggestive of a severe allergic reaction. Treatment requires careful assessment of the expected benefits and risks by an oncology team.

Before treatment, HER2 status should be confirmed using an appropriate validated test, and baseline cardiac function should be assessed. Patients with heart failure, reduced cardiac function, significant cardiovascular disease, or previous exposure to cardiotoxic chemotherapy require particular attention. Cardiac monitoring is generally continued at regular intervals during therapy and may be required after treatment, depending on the regimen and clinical circumstances. Trastuzumab should be used cautiously during pregnancy and breastfeeding, following the relevant product information and specialist advice. Interactions may be clinically important when trastuzumab is combined with chemotherapy, particularly anthracyclines, because of increased cardiac risk. As a monoclonal antibody, trastuzumab is not typically associated with the same metabolic drug interactions as many small-molecule medicines, but its combination with other anticancer therapies can alter overall safety. The complete medication list, prior cancer treatments, pregnancy status where relevant, and cardiac history should be reviewed before treatment.

Confirm the tumour's HER2 status, cancer indication, formulation, and prescribed regimen before dispensing or administration. Review baseline cardiac function and arrange repeat assessments according to the treatment protocol and current product information. Check previous or planned anthracycline exposure and consider additional cardiac evaluation for patients with cardiovascular risk factors. For intravenous treatment, follow the specific product instructions for reconstitution, dilution, storage, infusion rate, and observation; use subcutaneous formulations only according to their authorised administration instructions. Monitor patients during and after administration for infusion-related reactions, particularly during the initial dose. Counsel patients about symptoms of heart failure, respiratory complications, and severe allergic reactions, and explain when urgent medical attention is needed. Verify the intended trastuzumab product carefully and do not confuse it with other HER2-directed medicines or antibody-drug conjugates, which have different dosing and safety requirements. Coordinate care among oncology, pharmacy, nursing, and cardiac teams when clinically indicated.