TYKERB

What it is

TYKERB contains 405 mg of lapatinib ditosilate monohydrate per tablet, equivalent to 250 mg of lapatinib free base. Lapatinib is a member of the 4-anilinoquinazoline class of kinase inhibitors. Lapatinib is a potent, reversible, and selective inhibitor of the intracellular tyrosine kinase domains of both ErbB1 (EGFR) and HER2 (ErbB2) receptors.

Approved indications

— TYKERB in combination with an aromatase inhibitor is indicated for the treatment of post-menopausal women with hormone receptor-positive metastatic breast cancer whose tumours overexpress HER2 and for whom hormonal therapy is indicated. — TYKERB in combination with capecitabine is indicated for the treatment of patients with advanced or metastatic breast cancer whose tumours overexpress HER2 and whose tumours have progressed after treatment with an anthracycline and a taxane, and who have progressed on prior trastuzumab therapy in the metastatic setting. — TYKERB in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer whose tumours overexpress HER2 and for whom trastuzumab is not appropriate.

Dosing overview

The recommended dose of TYKERB in combination with capecitabine is 1250 mg once daily continuously. The recommended dose of TYKERB in combination with paclitaxel is 1500 mg once daily continuously. The recommended dose of TYKERB in combination with an aromatase inhibitor is 1500 mg once daily continuously. TYKERB should be taken at least one hour before, or at least one hour after food.

Key safety warnings

TYKERB has been associated with decreases in left ventricular ejection fraction (LVEF), and cardiac events including LVEF decreases were observed in patients who received TYKERB. LVEF should be evaluated in all patients prior to initiation of treatment and should continue to be evaluated during treatment at approximately 8–12 week intervals to ensure that LVEF does not decline to an unacceptable level. A concentration-dependent QTc interval increase has been observed, and electrocardiograms with QT measurement should be considered prior to administration of TYKERB and throughout treatment. Caution should be taken if TYKERB is administered to patients who have or may develop prolongation of QTc, including those with hypokalaemia or hypomagnesaemia, congenital long QT syndrome, or those taking anti-arrhythmic medicines; hypokalaemia, hypocalcaemia or hypomagnesaemia should be corrected prior to TYKERB administration. TYKERB has been associated with reports of interstitial lung disease and pneumonitis, and patients should be monitored for pulmonary symptoms indicative of these conditions. Hepatotoxicity (ALT or AST greater than 3 times the upper limit of normal and total bilirubin greater than 1.5 times the upper limit of normal) has been observed in clinical trials and post-marketing experience, may be severe, and deaths have been reported; hepatotoxicity may occur days to several months after initiation of treatment. Liver function tests should be monitored before initiation of treatment, every 4 to 6 weeks during treatment, and as clinically indicated; if changes in liver function are severe, therapy with TYKERB should be discontinued permanently. Patients who carry the HLA alleles DQA1*02:01 and DRB1*07:01 have increased risk of TYKERB-associated hepatotoxicity, with a risk of 8 percent in allele carriers compared to 0.5 percent in non-carriers. Diarrhoea, including severe diarrhoea, has been reported with TYKERB treatment and may be severe with deaths reported; diarrhoea generally occurs early during treatment, with almost half of patients with diarrhoea first experiencing it within 6 days, and usually lasts 4–5 days. Prompt treatment of diarrhoea with anti-diarrhoeal agents such as loperamide after the first unformed stool is recommended. Severe cutaneous reactions including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported with lapatinib; if these conditions are suspected, discontinue treatment.

Contraindications

TYKERB is contraindicated in patients with hypersensitivity to any of the ingredients.

PBS listing

In November 2015, the PBAC recommended a change to the TYKERB listing for metastatic (Stage IV) HER2-positive breast cancer, removing the restriction requiring that patients must not have received prior treatment with trastuzumab emtansine.

Regulatory history

TYKERB lapatinib 250 mg tablets were first registered on the ARTG on 28 June 2007. The TGA approved an application in June 2012 to extend TYKERB's indications, allowing its use in combination with paclitaxel for the first-line treatment of patients with metastatic breast cancer whose tumours overexpress HER2 and for whom trastuzumab is not appropriate.