Trastuzumab Emtansine

Trastuzumab emtansine is a targeted anticancer medicine classified as an antibody-drug conjugate (ADC). It combines trastuzumab, a monoclonal antibody that recognises human epidermal growth factor receptor 2 (HER2), with emtansine, a cytotoxic agent that disrupts microtubules and interferes with cell division. After binding to HER2 on cancer cells, the medicine is taken into the cell, where emtansine is released and damages the cellular structures required for division. The trastuzumab component also interferes with HER2-related signalling and contributes to immune-mediated antitumour activity. This targeted delivery approach is intended to concentrate the cytotoxic effect in HER2-expressing cancer cells, although healthy tissues can also be affected. Trastuzumab emtansine is administered by intravenous infusion under specialist supervision. It is primarily used in selected adults with HER2-positive breast cancer, including patients with residual invasive disease after neoadjuvant treatment and those with unresectable locally advanced or metastatic disease following previous therapy. Confirming HER2 status using an appropriate validated test is essential before treatment. The medicine is different from trastuzumab alone and from other HER2-targeted antibody-drug conjugates. Careful monitoring is required because treatment can cause liver injury, reduced platelet counts, cardiac dysfunction, lung toxicity and harm to an unborn baby.

Trastuzumab emtansine was developed as a HER2-targeted antibody-drug conjugate to deliver a cytotoxic agent to cancer cells expressing HER2. It received initial approval from the US Food and Drug Administration (FDA) on 22 February 2013 for selected patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. The European Commission granted marketing authorisation for Kadcyla on 15 November 2013. Subsequent approvals expanded its use to include adjuvant treatment of eligible adults with HER2-positive early breast cancer who have residual invasive disease following neoadjuvant HER2-targeted therapy and chemotherapy. Clinical development included the EMILIA trial in previously treated advanced breast cancer and the KATHERINE trial in patients with residual invasive disease after neoadjuvant treatment. These studies helped establish its role in different breast cancer treatment settings. Regulatory indications and eligibility criteria vary by country, so the current local prescribing information should be consulted before treatment.

Trastuzumab emtansine is used for selected adults with HER2-positive breast cancer. In the adjuvant setting, it is indicated for patients with residual invasive disease in the breast or lymph nodes after neoadjuvant taxane-based chemotherapy and HER2-targeted treatment. In unresectable locally advanced or metastatic breast cancer, it is used in eligible patients who have previously received trastuzumab and a taxane. Treatment selection depends on HER2 test results, disease stage, previous treatment, recurrence history and the applicable regulatory approval. Trastuzumab emtansine is generally administered as a single agent rather than as a routine combination with chemotherapy. It is not interchangeable with trastuzumab alone or trastuzumab deruxtecan, as these medicines have different compositions, dosing instructions and safety profiles.

Trastuzumab emtansine is administered by intravenous infusion, generally at a dose of 3.6 mg/kg every three weeks for approved adult indications. The first infusion is usually given over approximately 90 minutes, and subsequent infusions may be administered over about 30 minutes if earlier doses have been tolerated. For adjuvant treatment of early breast cancer, therapy is generally continued for a total of 14 cycles unless disease recurrence or unacceptable toxicity requires an earlier stop. For metastatic disease, treatment is usually continued until disease progression or unacceptable adverse effects. Dosing may need to be withheld, reduced or permanently discontinued for liver toxicity, thrombocytopenia, cardiac dysfunction or other serious reactions. Liver function, platelet counts and cardiac function should be assessed before treatment and monitored during therapy. The medicine must be reconstituted and administered by trained healthcare professionals according to the product instructions.

Common side effects of trastuzumab emtansine include fatigue, nausea, musculoskeletal pain, headache, constipation and increased liver enzyme levels. Reduced platelet counts, anaemia and other blood-related changes may also occur. Some patients experience nosebleeds, peripheral neuropathy or infusion-related symptoms. Side effects vary between individuals and may depend on previous treatments and overall health. Many can be managed through supportive care, laboratory monitoring and medically supervised dose adjustments. Patients should report persistent or worsening symptoms, unusual bruising, bleeding, numbness or tingling, and marked fatigue to their healthcare team.

Trastuzumab emtansine carries important risks, including severe liver injury, liver failure, reduced left ventricular ejection fraction and embryo-fetal toxicity. Thrombocytopenia can lead to serious bleeding, while peripheral neuropathy may require treatment interruption or dose modification. Interstitial lung disease and pneumonitis have also been reported and can be serious. Infusion-related reactions and hypersensitivity may occur. Rare cases of nodular regenerative hyperplasia of the liver have been reported and may require permanent discontinuation. Liver function and cardiac function must be assessed before and during treatment, with platelet counts monitored before each dose. Treatment should be withheld or discontinued according to the severity of the adverse reaction and the applicable prescribing information. Pregnancy should be avoided during treatment and for the recommended period after the final dose because of the risk of fetal harm.

Before starting treatment, clinicians should confirm HER2 positivity using an appropriate validated test and assess liver function, platelet counts, cardiac function and existing neurological symptoms. Patients with significant liver disease, pre-existing cardiac dysfunction or low platelet counts may require additional assessment. Medicines that increase bleeding risk, including anticoagulants and antiplatelet agents, should be reviewed carefully because thrombocytopenia can increase bleeding risk. Other medicines that may affect liver function also warrant review. Trastuzumab emtansine is an antibody-drug conjugate, so its interaction profile differs from that of many conventional small-molecule medicines; however, interactions and overlapping toxicities remain clinically important. Pregnancy and breastfeeding require specialist counselling, and effective contraception should be used according to the current product information. Patients should disclose all prescription medicines, non-prescription products and supplements to their healthcare team.

Confirm HER2 status and the patient's treatment history before prescribing trastuzumab emtansine. Document baseline liver function, platelet counts, cardiac function and peripheral neurological symptoms. Monitor liver enzymes, bilirubin and platelet counts before each dose, and reassess cardiac function at intervals recommended by the applicable prescribing information. Counsel patients to report jaundice, dark urine, unusual bleeding, breathlessness, new swelling, worsening numbness or tingling, and symptoms suggestive of an infusion reaction. Ensure correct product identification because trastuzumab emtansine must not be substituted for trastuzumab alone or other HER2-targeted conjugates. Pharmacy and infusion teams should follow the product-specific reconstitution, handling and administration instructions. Dose interruptions, reductions and discontinuation should be guided by the type and severity of toxicity and the relevant clinical guidance.