Dr. Pegram on Combining Trastuzumab and Pertuzumab

Mark D. Pegram, MD, a professor of medicine at Stanford University Medical Center and the director of the Breast Cancer Program at the Stanford Cancer Institute, describes the combination of pertuzumab and trastuzumab as a treatment for patients with HER2-positive metastatic breast cancer.

The monoclonal antibodies pertuzumab and trastuzumab have unique mechanisms of action that synergistically accomplish a dual blockade of the HER2 growth factor. These agents bind to different epitopes, allowing their use in combination. Pertuzumab binds to the dimerization interface, blocking the ability of HER2 from directly binding to HER3 while trastuzumab binds to the surface of HER2 and prevents ligand-independent dimerization.

The combination of pertuzumab with trastuzumab and docetaxel was shown to be superior to trastuzumab and docetaxel alone, Pegram notes. This was shown in the phase III CLEOPATRA trial, which led to the FDA approval of this combination for patients who have not received prior treatment for HER2-positive metastatic breast cancer.