Harbeck, Nadia; Beckmann, Matthias W.; Rody, Achim; Schneeweiss, Andreas; Müller, Volkmar; Fehm, Tanja; Marschner, Norbert; Gluz, Oleg; Schrader, Iris; Heinrich, Georg; Untch, Michael; Jackisch, Christian
HER2 Dimerization Inhibitor Pertuzumab - Mode of Action and Clinical Data in Breast Cancer.
In: Breast Care, No. 1: pp. 49-55
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.