Early proof-of-concept studies presented at ASCO show RAD001 (everolimus) may offer a novel treatment strategy for breast cancer by enhancing the efficacy of, and overcoming resistance to, several commonly used breast cancer treatments.

Findings from a phase II study show that RAD001 enhances tumour shrinkage when given in combination with letrozole (Femara) to postmenopausal women with newly diagnosed estrogen receptor-positive (ER+) breast cancer. Further, initial results from two phase I trials in which RAD001 was combined with trastuzumab (Herceptin) and chemotherapy agents suggest that the addition of RAD001 overcame resistance to trastuzumab. The combination appears highly active, achieving complete responses in a few patients and partial responses or stable disease in a majority of patients.

These results were among several studies of RAD001 presented at the 44th annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois, US. Findings of a phase III trial in metastatic renal cell carcinoma showing that RAD001 more than doubled the time without tumour growth after failure of standard treatments were presented earlier in the meeting. RAD001 is an investigational once-daily oral therapy that may offer a new approach to cancer treatment by continuously inhibiting the mTOR protein, a central regulator of tumour cell division and blood vessel growth in cancer cells.

"The mTOR pathway is a major route to resistance in targeted cancer therapies, and the early data in combination with Herceptin and chemotherapy demonstrate proof of concept that by inhibiting mTOR we may be able to overcome resistance to these medicines," said David Epstein, CEO and President of Novartis Oncology. "These remarkable early findings support exploring the potential of RAD001 in addressing unmet medical needs in women with HER2+ breast cancer in a larger randomized clinical trial."

For breast cancer patients whose disease becomes resistant to available drugs, identifying the mechanism of resistance is important for restoring activity to treatment. Preclinical studies have shown that RAD001, an inhibitor of mTOR, acts on the pathway that mediates trastuzumab resistance and has the potential to help restore response in patients who are refractory to therapy. RAD001 works through direct antitumour activity as well as through its influence on two of the most important pathways for breast cancer, the estrogen receptor and the HER2/neu pathways.
Based on these data, Novartis will initiate a new trial to evaluate the potential of RAD001 in breast cancer in early 2009. Plans for this trial are ongoing and will be announced at a later date.

"In patients with hormone-sensitive breast cancer, the results from the randomized Phase II study are exciting because they show that adding RAD001 to initial treatment with letrozole may improve outcomes for early-stage breast cancer patients," said Professor Jose Baselga, MD, Hospital Vall D'Hebron, Barcelona, Spain. "Taken together, the results of the three trials announced today indicate that RAD001 has a promising potential across various subsets of breast cancer."

RAD001, an oral inhibitor of mTOR, is an investigational drug being studied in multiple tumour types. In cancer cells, RAD001 inhibits mTOR, a protein that acts as a central regulator of tumour cell division, cell metabolism and blood vessel growth. RAD001 is a once-daily oral therapy that provides continuous inhibition of mTOR.

In addition to breast cancer, RAD001 is presently being evaluated in renal cell carcinoma; neuroendocrine tumours; lymphoma, lung, stomach and liver cancers, in addition to other cancers; and in tuberous sclerosis complex as a single agent or in combination with existing cancer therapies.

As an investigational compound, the safety and efficacy profile of RAD001 has not yet been established in oncology. Access to RAD001 is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the compound. Because of the uncertainty of clinical trials, there is no guarantee that RAD001 will ever be commercially available for oncology indications anywhere in the world. Everolimus is approved 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 and is available in more than 60 countries.

Femara is a leading once-daily oral aromatase inhibitor available in more than 90 countries, including the US, major European markets, and Japan.