Phase III Trial Planned for RAD001 with Herceptin-Chemo Combo

Investigational agent RAD001 (everolimus) made news recently for its activity in kidney cancer. But now two early phase I trials have also shown the drug may have benefit in breast cancer, which is paving the way for a phase III trial in the near future.

Herceptin (trastuzumab), which was first approved for metastatic HER2-positive breast cancer in 1998, blocks the epidermal growth factor receptor 2, but most women’s cancer becomes resistant to the monoclonal antibody over time, and eventually their disease recurs or progresses. RAD001 is an mTOR inhibitor, which was developed to block a different growth pathway inside cancer cells.

While phase I studies are small and designed to determine the best dose and safety, anti-cancer activity was noted in the trials. Both studies looked at whether RAD001 could help women’s cancer become sensitive to Herceptin treatment again. One study, which looked at 22 evaluable patients from the 27 total enrolled in the trial, showed that the combination of RAD001 and Herceptin along with weekly Taxol (paclitaxel) stopped the disease from advancing in 17 of the 27 patients, including one patient who eventually had no evidence of disease.

In the second study, 34 patients were treated with the targeted agents combined with another chemotherapy, Navelbine (vinorelbine). The three-drug combo controlled the disease in 21 of the 34 patients. Severe side effects were noted, which included neutropenia, which increases risk of infection, and mouth sores.

All patients had been heavily pre-treated and had become resistant to Herceptin therapy, with some women also becoming resistant to taxane therapy, including Taxol. Positive results in these two studies have led to an international phase III study planned for a combination of RAD001, Herceptin, and Taxol. RAD001 is also being studied in lymphoma, neuroendocrine cancers, and is expected to be approved for kidney cancer in early 2009.