HER2 Dimerization Inhibitor Pertuzumab - Mode of Action and Clinical Data in Breast Cancer

The humanized monoclonal antibody pertuzumab prevents the
dimerizationof HER2 with other HER receptors, in particular the
pairing of the mostpotent signaling heterodimer HER2/HER3, thus
providing a potent strategyfor dual HER2 inhibition. It binds to
the extracellular domain of HER2at a different epitope than
trastuzumab. Pertuzunnab and trastuzumab actin a complementary
fashion and provide a more complete blockade ofHER2-mediated signal
transduction than either agent alone. Phase IIstudies demonstrated
that pertuzunnab was generally well tolerated as asingle agent or
in combination with trastuzumab and/or cytotoxic agents,and implied
an improved clinical efficacy of the combination ofpertuzumab and
trastuzumab in early and advanced HER2-positive breastcancer.
Results of the pivotal phase III study CLEOPATRA in patientswith
HER2-positive metastatic breast cancer demonstrated that
theaddition of pertuzumab to first-line combination therapy with
docetaxeland trastuzumab significantly prolonged progression-free
and overallsurvival without increasing cardiac toxicity. Currently,
the combinationof both antibodies is being explored in the
palliative setting as wellas in the treatment of early
HER2-positive breast cancer. Dual HER2inhibition with the HER2
dimerization inhibitor pertuzumab andtrastuzumab may change
clinical practice in HER2-positive first-linemetastatic breast
cancer treatment.