Dr. Baselga on Combining Pertuzumab with Trastuzumab

José Baselga, MD, PhD, a professor in the Department of Medicine at Harvard Medical School and chief of Hematology/Oncology at Massachusetts General Hospital, discusses combining (Perjeta) with trastuzumab (Herceptin).

The two antibodies work together because they have complementary mechanisms of action. HER2 signals via two main mechanisms, one of which is via ligand-independent HER2 activation. This mechanism is blocked by trastuzumab.

Another activation of HER2 is the formation of dimers with other members of the HER2 family of receptors and, most importantly, with HER3. HER3 plays a critical role in HER2 signaling. The ligand binds to HER3, HER3 gets close to HER2, they dimerize, and they signal. This interaction is blocked by pertuzumab.

By adding pertuzumab and trastuzumab together, the two known mechanisms of HER2 activation are blocked.

The unique ability of pertuzumab plus trastuzumab to target HER2 led to the FDA approval of the combination with docetaxel on June 8, 2012, for people with HER2-positive metastatic breast cancer who have not received prior therapy.