Researchers involved in an international multicenter trial have reported that neratinib is active for the treatment of patients with advanced HER2-positive breast cancer who have or have not received Herceptin® (trastuzumab). The details of this study were published in the March 10, 2010 issue of the Journal of Clinical Oncology.[1]

Twenty to 25% of breast cancers overexpress HER2. Overexpression of this protein leads to increased growth of cancer cells and a worse breast cancer prognosis. Herceptin is currently the only drug FDA-approved specifically to target HER2-positive breast cancer. Neratinib is an investigational oral medication that targets HER2 as well as HER4 and the epidermal growth factor receptor (EGFR).

The current study included 136 patients with advanced HER2-positive breast cancer treated with neratinib. Seventy patients were Herceptin-naïve, and 66 had received prior Herceptin.

• The response rate was 24% for patients who had received prior Herceptin with a 16-week progression-free survival (PFS) rate of 59% and a median PFS of 22.3 weeks.
• The response rate was 56% for patients who had not received prior Herceptin with a 16-week PFS rate of 78% and a median PFS rate of 39.6%.
• Diarrhea was more common in patients receiving prior Herceptin.

Comments: These and other studies suggest that neratinib will be an important drug for the treatment of HER2-positive breast cancer. A Phase III clinical trial is underway comparing Taxol and neratinib to Herceptin plus Taxol for the initial treatment of advanced, HER2-positive breast cancer.

Reference:
[1] Burstein HJ, Sun Y, Dirix LY, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB-positive breast cancer. Journal of Clinical Oncology. 2010;28:1301-1307.