New data from two early clinical studies show that Afinitor (everolimus) may overcome resistance to Herceptin (trastuzumab) in women with HER2- positive metastatic breast cancer. These results support the initiation of a phase III clinical trial programme to fully explore the potential of Afinitor, also known as RAD001, in breast cancer.

Two PHASE I studies were presented during the CTRC-AACR San Antonio Breast Cancer Symposium. Initial results from both studies were released earlier this year at the American Society of Clinical Oncology (ASCO) annual meeting.

Updated results from the first phase I trial show that the combination of Afinitor with Herceptin and weekly Taxol (paclitaxel) halted tumour growth in 77 per cent of patients with HER2-positive metastatic breast cancer with documented resistance to Herceptin. In addition, the data demonstrated the first complete response in the trial.

In addition, updated data from the second Phase I study show promising anticancer activity for Afinitor in combination with Herceptin and Navelbine (vinorelbine) in heavily pretreated Herceptin-resistant patients with HER2-positive metastatic breast cancer. In the study, Afinitor in combination with Herceptin and Navelbine halted tumour growth in 62 per cent of patients.

"Data presented at this meeting affirm the potential of Afinitor to reverse Herceptin resistance and restore patient response to treatment," said Ruth O'Regan, MD, Emory University School of Medicine, Atlanta, GA. "These findings are important for patients with HER2-positive metastatic breast cancer who develop resistance to Herceptin."

Preclinical data have shown that Afinitor, an inhibitor of mTOR, acts on the pathway that mediates Herceptin resistance and has the potential to help restore response in these patients. Afinitor works through direct antitumour activity and through its influence on two of the most important pathways for breast cancer, the erbB receptor and the HER2 pathways.

"We are encouraged by the benefit Afinitor provided to advanced breast cancer patients in these early trials," said Alessandro Riva, MD, executive vice president & Global Head of Development, Novartis Oncology. "Novartis is committed to further evaluating the potential of Afinitor in combination with Herceptin as a new treatment regimen in breast cancer, as well as to studying its role in treating other tumour types."

Novartis will initiate a worldwide phase III clinical trial programme to further evaluate the potential of Afinitor in combination with Herceptin and chemotherapy in patients with HER2-positive metastatic breast cancer.

Afinitor, an oral once-daily inhibitor of mTOR, is an investigational drug being studied in multiple tumour types. In cancer cells, Afinitor provides continuous inhibition of mTOR, a protein that acts as a central regulator of tumour cell division, cell metabolism and blood vessel growth.

The safety and efficacy profile of Afinitor has not yet been established in oncology and there is no guarantee that Afinitor will become commercially available for oncology indications. The active ingredient in Afinitor is everolimus, which is available in different dosage strengths under the trade name Certican for the prevention of organ rejection in heart and kidney transplant recipients. Certican was first approved in the EU in 2003.

In addition to breast cancer, Afinitor is being evaluated as a single agent or in combination with existing therapies in renal cell carcinoma, neuroendocrine tumours, lymphoma, gastric, lung and other cancers, as well as tuberous sclerosis complex.