Lapatinib

Lapatinib is an oral targeted anticancer medicine belonging to the tyrosine kinase inhibitor class. It works by blocking the activity of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), proteins involved in cell signalling and the growth of certain cancers. Some breast cancers produce excessive amounts of HER2, which can promote tumour growth and progression. By inhibiting these signalling pathways, lapatinib may slow the growth of cancer cells. It is supplied as tablets and is used in selected patients with HER2-positive advanced or metastatic breast cancer, usually in combination with other anticancer medicines. Depending on the applicable regulatory approval and clinical situation, combinations may include capecitabine, an aromatase inhibitor such as letrozole, or trastuzumab. Tumour HER2 status and hormone receptor status help determine whether treatment is appropriate. Lapatinib is not suitable for every person with breast cancer, and the choice of combination depends on previous treatments, disease characteristics, and patient-specific factors. Important safety considerations include diarrhoea, liver injury, skin reactions, and possible effects on heart function and heart rhythm. Regular clinical assessment and laboratory monitoring help identify complications early. Treatment should be prescribed and supervised by an oncology specialist.

Lapatinib was developed as a targeted treatment for cancers driven by HER2 and EGFR signalling. It inhibits the intracellular tyrosine kinase domains of these receptors, reducing signals involved in tumour cell growth and survival. The United States Food and Drug Administration (FDA) first approved lapatinib in 2007 for selected patients with advanced or metastatic HER2-positive breast cancer in combination with capecitabine. The European Commission granted marketing authorisation for Tyverb in the European Union on 10 June 2008, initially under conditional approval; the authorisation became full in February 2015. Subsequent regulatory decisions established additional combination-treatment indications in selected patients, including use with an aromatase inhibitor or trastuzumab in relevant settings. Clinical development included studies evaluating lapatinib with capecitabine and endocrine therapy in HER2-positive advanced breast cancer. The precise approved indications differ between countries, so current local prescribing information should be consulted before treatment is selected.

Lapatinib is used for selected adults with HER2-positive advanced or metastatic breast cancer. Depending on local approval and the patient's clinical circumstances, it may be combined with capecitabine after progression following previous treatment that included an anthracycline, a taxane, and trastuzumab in the metastatic setting. In some jurisdictions, it may be used with an aromatase inhibitor for postmenopausal patients with hormone receptor-positive, HER2-positive metastatic disease, or with trastuzumab in selected patients whose hormone receptor-negative metastatic disease has progressed following previous trastuzumab-based treatment. Tumour HER2 status should be established using an appropriate validated test, and hormone receptor status should be considered when selecting treatment. Lapatinib is generally used as part of a combination regimen rather than as routine standalone treatment. Suitability depends on previous therapy, disease characteristics, treatment goals, tolerability, and the applicable regulatory indication.

Lapatinib is taken orally as tablets, usually once daily. The commonly used adult dose is 1,250 mg daily when combined with capecitabine, 1,500 mg daily when combined with an aromatase inhibitor, or 1,000 mg daily when combined with trastuzumab under applicable product information. These regimens are not interchangeable, and the correct dose must be determined from the approved indication and local prescribing guidance. Lapatinib tablets should generally be taken at least one hour before or one hour after food, and the full daily dose should be taken together rather than divided. Capecitabine and other combination medicines follow their own administration schedules. Treatment may continue while clinical benefit persists and adverse effects remain manageable. Dose interruption or reduction may be necessary for diarrhoea, liver abnormalities, cardiac effects, or drug interactions. Patients should not change the dose without specialist guidance.

Common side effects of lapatinib include diarrhoea, nausea, vomiting, reduced appetite, fatigue, skin rash, indigestion, and abdominal discomfort. When used with capecitabine, redness, tenderness, tingling, or peeling of the palms and soles may occur. Some patients develop dry skin, mouth irritation, or changes in liver blood tests. Side effects vary according to the treatment combination and individual health status. Diarrhoea can begin early and may become serious if fluids and electrolytes are lost. Patients should report persistent diarrhoea, difficulty maintaining fluid intake, worsening skin reactions, or symptoms that interfere with daily activities. Supportive care and clinician-directed dose changes may help manage adverse effects. Patients should not discontinue treatment or start additional medicines for side effects without discussing the situation with their healthcare team.

Important risks associated with lapatinib include severe liver injury, reduced left ventricular ejection fraction, QT interval prolongation, severe diarrhoea with dehydration, interstitial lung disease or pneumonitis, and serious skin reactions. Liver injury can occasionally be life-threatening, so liver function should be checked before treatment and periodically during therapy. Heart function should be assessed before treatment and monitored as clinically indicated. Electrocardiograms and electrolyte measurements may be necessary for patients at risk of QT prolongation. Severe or persistent diarrhoea, fainting, palpitations, new breathlessness, yellowing of the skin or eyes, dark urine, or a rapidly worsening rash require prompt medical assessment. Severe hypersensitivity is a contraindication. Depending on the type and severity of toxicity, treatment may need to be interrupted, reduced, or permanently discontinued. Patients should receive clear instructions on when to contact their oncology team or seek urgent care.

Before starting lapatinib, clinicians should review liver function, cardiac history, current medicines, electrolyte levels, pregnancy status where relevant, and the planned combination regimen. Particular caution is required in patients with pre-existing liver disease, impaired cardiac function, prolonged QT interval, or low potassium or magnesium levels. Lapatinib is metabolised mainly through CYP3A4, so strong CYP3A4 inhibitors may increase its exposure and strong inducers may reduce its effectiveness. Medicines that prolong the QT interval or affect cardiac function require careful review. Acid-reducing medicines may also alter lapatinib absorption. Patients should tell their healthcare team about prescription medicines, over-the-counter products, supplements, and herbal preparations. Lapatinib can cause fetal harm, so pregnancy prevention and reproductive counselling are important during treatment. Breastfeeding should be discussed with the treating specialist. Dose adjustments or additional monitoring may be needed in severe hepatic impairment.

Confirm HER2 status, the precise approved indication, and the intended combination regimen before prescribing or dispensing lapatinib. Verify the daily dose and meal-timing instructions, and explain that the tablets should be taken together as one daily dose. Review all medicines for CYP3A4 interactions, QT-prolonging effects, and potential effects on absorption. Check baseline liver function and cardiac status, including left ventricular ejection fraction, and arrange follow-up testing according to the product information and the patient's risk profile. Explain how to recognise diarrhoea early and when to seek help for dehydration, breathing problems, jaundice, palpitations, or severe skin reactions. Reinforce adherence to the prescribed schedules for combination medicines, particularly capecitabine. Dose changes should be guided by the treating oncology team, and severe liver injury requires particular caution regarding future exposure. Coordinate toxicity management and treatment-response assessments across the oncology and pharmacy teams.