The European Medicines Agency (EMA) has granted an update to the marketing authorisation for Tyverb® (lapatinib) to be used in combination with Herceptin® (trastuzumab).
This combination is indicated for adult patients with breast cancer whose tumours overexpress HER2 (ErbB2) with hormone receptor-negative (HR-) metastatic disease that has progressed on prior trastuzumab therapy(ies) in combination with chemotherapy.
"We are proud to bring a new chemotherapy-free option to metastatic breast cancer patients. Through vertical dual blockade of the HER2 receptor, the combination of lapatinib and trastuzumab achieves a clinically significant improvement in overall survival for patients with HER2-positive, HR-negative metastatic breast cancer,” said Dr Pim Kon, UK Medical Director, GlaxoSmithKline.
“We believe this new combination therapy has the potential to make a meaningful impact on the care and survival of women in this breast cancer population.”
'Above & below' the cell membrane
The combination works by targeting the same HER2 receptor at different points – ‘above’ and ‘below’ the cell membrane (vertical) thereby enhancing blockade2 – these agents subsequently produce a vertical dual blockade of the HER2 receptor:
•Trastuzumab is a monoclonal antibody that binds to the extracellular (‘above’) domain of the HER2 receptor.
•Lapatinib, in contrast, inhibits tyrosine kinase activity of the same HER2 receptor intracellularly (‘below’).
By targeting both extracellular and intracellular domains of the same receptor [vertical dual HER2 blockade] complementary mechanisms of action may be realised, potentially achieving better pathway inhibition than could be accomplished with either compound alone.
The EMA approval is based on findings from the EGF104900 study – a randomised, open-label, Phase III study of lapatinib plus trastuzumab versus lapatinib monotherapy in patients with HER2-positive metastatic breast cancer whose disease had progressed on a trastuzumab-containing regimen. The primary endpoint of the trial was progression-free survival (PFS), with overall survival (OS) as the secondary endpoint.
Limited therapy options for HER2
Approximately 25% to 30% of women with metastatic breast cancer have tumours which over-express ErbB2, a protein commonly referred to as HER2 (human epidermal growth factor). HER2-positive tumours are associated with a worse prognosis and reduced overall survival compared to HER2-negative tumours.
Patients with HER2 advanced or metastatic breast cancer have limited targeted therapy options available to them after trastuzumab-based therapy has failed to halt disease progression. GlaxoSmithKline is working with the National Health Service (NHS) to support decision-making about the most appropriate funding route for this new treatment combination of lapatinib and trastuzumab.