GlaxoSmithKline announced positive data from the first-ever randomised, multi-centre, open label phase III trial of the combination of two targeted agents, lapatinib and trastuzumab, in women with HER2-positive metastatic breast cancer. HER2-positive breast cancer is a particularly aggressive form of cancer that affects approximately 25 to 30 per cent of breast cancer patients.

The study results demonstrated a benefit from the combination. Both treatments target the HER2 protein but work in different ways. Trastuzumab attaches to the outside of the HER2 protein, while lapatinib goes inside the cell to block signals from the HER2 protein for the cancer to grow.

According to a press release, GlaxoSmithKline Oncology will present these and other new data in breast cancer at the annual American Society of Clinical Oncology (ASCO) meeting in Chicago beginning Friday 30th May.

"Many women with HER2 positive breast cancer are still very active and living full lives, yet when their disease progresses after trastuzumab and chemotherapy, we have had limited treatment options. Therefore it is important to study options that may eventually help women in their fight against this disease," said lead investigator Joyce O'Shaughnessy, M.D., Baylor-Sammons Cancer Center, Texas Oncology, PA, US Oncology, Dallas, TX. "Effectively attacking HER2 from multiple angles is an exciting and innovative approach, and demonstrates the significant advances being achieved in treating this complex form of breast cancer."

Despite receiving multiple prior lines of anti-cancer therapy, patients who received lapatinib plus trastuzumab in this study experienced: A statistically significant increase in median progression-free survival versus lapatinib alone (12 weeks vs. 8.1 weeks); A 27 per cent reduction in the risk of disease progression [Hazard Ratio: 0.73; p=0.008]; A response rate of 10.3 per cent versus 6.9 per cent. Response rate is a clinical term that is calculated by complete and partial disappearance of the tumour. Double the overall clinical benefit rate versus lapatinib alone (24.7 per cent vs. 12.4 per cent; p=0.01). Clinical benefit rate is calculated by the response rate and the rate of durable stable disease (greater than or equal to 6 months); A trend in improved overall survival [Hazard Ratio: 0.75; p=0.106].

The study also demonstrated the activity of lapatinib as a single agent in this patient population, with patients on this arm achieving a median progression free survival of 8.1 weeks and an overall clinical benefit rate of 12.4 per cent.

The clinical synergy of lapatinib and trastuzumab confirms previous observational findings in preclinical studies and previously reported data from a phase I study. These latest findings confirm the rationale for further research of this combination in earlier lines of therapy in the metastatic setting and in early stage disease. Additional analysis is underway to explore the benefit that lapatinib plus trastuzumab can offer to less heavily pre-treated patients.

Lapatinib is an oral small-molecule inhibitor of the HER2 (ErbB2) tyrosine kinase receptor. Stimulation of HER2 is associated with cell proliferation and with multiple processes involved in tumour progression and metastases. Overexpression of this receptor has been reported in a variety of human tumours and is associated with poor prognosis and reduced overall survival.

On March 13, 2007, the United States Food and Drug Administration (FDA) approved lapatinib, in combination with capecitabine, for the treatment of patients with advanced or metastatic breast cancer whose tumours overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Lapatinib recently received a positive opinion from the Committee for Medical Products for Human Use (CHMP) of Europe. Marketing authorisation in Europe is pending.