GlaxoSmithKline (GSK) announced that the European Commission has granted a conditional marketing authorisation for Tyverb (lapatinib), the firstoral, small molecule dual targeted therapy, for all 27 European Union (EU) member states.
Lapatinib, in combination with capecitabine, is indicated for the treatment of patients with advanced or metastatic breast cancer whose tumours overexpress ErbB2 (HER2). Patients should have progressive disease following prior therapy, which must include anthracyclines and taxanes, and therapy with trastuzumab in the metastatic setting.
Today's news means that GSK is able to make lapatinib available in the European Union (subject to market access requirements) and the company is currently working with local regulatory authorities to ensure lapatinib is available to eligible patients as soon as possible, a GSK press release stated.
Lapatinib has a novel mechanism of action that is different from current licensed targeted therapies for ErbB2-positive disease. It is a small molecule that is administered orally and works by getting inside the cancer cell and inhibiting two receptor proteins - the tyrosine kinase components of the ErbB1 and ErbB2 receptors. The signalling of these receptors is responsible for tumour growth and proliferation.
"Today's news will benefit women across Europe with HER2-positive advanced or metastatic breast cancer which needs further treatment after the previous standard treatments of anthracyclines, taxanes, and trastuzumab. Lapatinib will play a valuable role in treating this especially aggressive form of advanced breast cancer, with the added benefit of convenience being a pill rather than needing intravenous administration" said Professor David Cameron, Co-Principle Investigator of the phase III trial (EGF100151) and Director of National Cancer Research Network; Chair, Medical Oncology, Faculty of Medicine and Health, University of Leeds.
"This news signifies a genuine advancement in the treatment of ErbB2-positive breast cancer. These patients are in real need of alternative therapies and we at GSK are proud to make this important new treatment option available to them," said Dr Paolo Paoletti, SVP and Global Head of the Oncology Medicine Development Centre at GSK. "The authorisation of lapatinib demonstrates our strong commitment to the discovery and development of novel anti-cancer treatments. With numerous clinical trials assessing lapatinib across a range of tumour types, we hope this is just the beginning for this innovative product, in terms of the positive difference it can make to patients' lives."
The authorisation was based on a pivotal phase III trial (EGF100151) in which women with locally advanced or metastatic ErbB2-positive breast cancer whose disease had progressed following prior treatment with anthracyclines, taxanes and trastuzumab were given either the combination of lapatinib and capecitabine, or capecitabine alone. The data showed that the investigator assessed median time to progression was 5.5 months (23.9 weeks) in the lapatinib and capecitabine arm versus 4.2 months (18.3 weeks) in the capecitabine arm alone (hazard ratio 0.72; p=0.008).1 The independent assessment demonstrated that lapatinib when given in combination with capecitabine significantly increased time to progression by 6.2 months (27.1 weeks) compared to 4.3 months (18.6 weeks) with capecitabine alone (hazard ratio 0.57 p=0.001).
Central nervous system metastases are a major burden for breast cancer patients. [5] In addition to the achievement of the primary endpoint in the pivotal phase III trial, results from an unplanned retrospective exploratory analysis demonstrated a reduced incidence of brain metastases as the first site of disease recurrence. In this retrospective exploratory analysis, 2% of patients in the combination arm had relapse to the brain compared with 6% in the capecitabine alone arm. These preliminary results with the addition of lapatinib are encouraging and are the basis of ongoing research in this area.
A conditional marketing authorisation is granted to a medicinal product with a positive benefit/risk assessment that fulfils an unmet medical need when the benefit to public health of its immediate availability outweighs the risk inherent in the fact that additional data are still required. A conditional marketing authorisation is renewable annually.As part of the conditions of the conditional marketing authorisation, GSK will provide further data from the pivotal study, and also conduct an additional clinical study.