NERLYNX

What it is

NERLYNX contains neratinib maleate, equivalent to 40 mg neratinib, presented as film-coated tablets. Neratinib is an irreversible inhibitor of three epidermal growth factor receptors: EGFR, HER2, and HER4. Neratinib binds to the HER2 receptor, reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signalling pathways, and inhibits tumour cell proliferation in vitro.

Approved indications

— Extended adjuvant treatment of adult patients with early-stage human epidermal growth factor receptor 2 (HER2)-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

Dosing overview

The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) taken orally once daily, continuously for one year. NERLYNX should be taken with food, preferably in the morning. The tablets should be swallowed whole, preferably with water, and should not be chewed, crushed, split or dissolved prior to swallowing. Patients should initiate treatment within 1 year after completion of trastuzumab-based therapy. The diarrhoea associated with NERLYNX can be managed with either anti-diarrhoeal prophylaxis during the first 56 days of treatment and initiated with the first dose of NERLYNX, or by a two week NERLYNX dose escalation approach prior to initiation of the recommended NERLYNX treatment regimen.

Key safety warnings

Diarrhoea has been reported during treatment with NERLYNX. The diarrhoea may be severe and associated with dehydration. Diarrhoea generally occurs early during the first or second week of treatment with NERLYNX and may be recurrent. Severe diarrhoea occurrences, despite prophylaxis treatment, should be aggressively managed with additional anti-diarrhoeal agents, electrolytes and fluids replacement, and/or interruption, reduction, or discontinuation of therapy with NERLYNX. Left ventricular dysfunction has been associated with HER2 inhibition. NERLYNX has not been studied in patients with less than lower limit of normal left ventricular ejection fraction (LVEF) or with significant cardiac history. In patients with known cardiac risk factors, conduct cardiac monitoring, including assessment of LVEF, as clinically indicated. Hepatotoxicity has been reported in patients treated with NERLYNX. Liver function tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin should be monitored at 1 week, then monthly for the first 3 months and every 6 weeks thereafter while on treatment or as clinically indicated. NERLYNX is associated with skin and subcutaneous tissue disorders. Patients with symptomatic skin and subcutaneous tissue disorders should be carefully monitored. Patients with renal impairment are at a higher risk of complications of dehydration if they develop diarrhoea, and these patients should be carefully monitored.

Contraindications

Hypersensitivity to the active substance or to any of the excipients contained in NERLYNX. Co-administration with the following medical products that are strong inducers of the CYP3A4/Pgp isoform of cytochrome P450: carbamazepine, phenobarbital, phenytoin (antiepileptics); St John's wort (Hypericum perforatum) (herbal product); rifampin (antimycobacterial). Severe hepatic impairment (Child-Pugh C).

Regulatory history

Nerlynx was approved by the TGA on 14 March 2019 for the extended adjuvant treatment of early-stage HER2-positive breast cancer following trastuzumab-based therapy. The TGA evaluation found the quality, nonclinical, and clinical data, including pharmacokinetics and efficacy from the ExteNET trial, to be largely adequate. Minor nonclinical deficiencies were noted but deemed not to preclude registration given the clear patient benefits.