HER2 Dimerization Inhibitor Pertuzumab - Mode of Action and Clinical Data in Breast Cancer.
The humanized monoclonal antibody pertuzumab prevents the dimerization of HER2 with other HER receptors, in particular the pairing of the most potent signaling heterodimer HER2/HER3, thus providing a potent strategy for dual HER2 inhibition. It binds to the extracellular domain of HER2 at a different epitope than trastuzumab. Pertuzumab and trastuzumab act in a complementary fashion and provide a more complete blockade of HER2-mediated signal transduction than either agent alone. Phase II studies demonstrated that pertuzumab was generally well tolerated as a single agent or in combination with trastuzumab and/or cytotoxic agents, and implied an improved clinical efficacy of the combination of pertuzumab and trastuzumab in early and advanced HER2-positive breast cancer. Results of the pivotal phase III study CLEOPATRA in patients with HER2-positive metastatic breast cancer demonstrated that the addition of pertuzumab to first-line combination therapy with docetaxel and trastuzumab significantly prolonged progression-free and overall survival without increasing cardiac toxicity. Currently, the combination of both antibodies is being explored in the palliative setting as well as in the treatment of early HER2-positive breast cancer. Dual HER2 inhibition with the HER2 dimerization inhibitor pertuzumab and trastuzumab may change clinical practice in HER2-positive first-line metastatic breast cancer treatment.
Brustzentrum, Frauenklinik, Universität München (LMU), Klinikum Offenbach, Germany.
Nadia
N
Harbeck
Frauenklinik, Universität Erlangen, Klinikum Offenbach, Germany.
Matthias W
MW
Beckmann
Klinik für Frauenheilkunde und Geburtshilfe Lübeck, Universitätsklinikum Schleswig-Holstein, Klinikum Offenbach, Germany.
Achim
A
Rody
Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg, Klinikum Offenbach, Germany.
Andreas
A
Schneeweiss
Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-Eppendorf, Klinikum Offenbach, Germany.
Volkmar
V
Müller
Frauenklinik, Universitätsklinikum Tübingen, Klinikum Offenbach, Germany.
Tanja
T
Fehm
Praxis für Interdisziplinäre Onkologie und Hämatologie, Freiburg i.Br., Klinikum Offenbach, Germany.
Norbert
N
Marschner
Westdeutsche Studiengruppe GmbH, Brustzentrum Niederrhein, Evangelisches Krankenhaus Bethesda, Mönchengladbach, Klinikum Offenbach, Germany.
Oleg
O
Gluz
Gynäkologisch-Onkologische Schwerpunktpraxis, Hannover, Klinikum Offenbach, Germany.
Iris
I
Schrader
Gynäkologisch-Onkologische Schwerpunktpraxis, Fürstenwalde, Klinikum Offenbach, Germany.
Georg
G
Heinrich
Klinik für Gynäkologie, HELIOS Klinikum Berlin-Buch, Klinikum Offenbach, Germany.
Michael
M
Untch
Klinik für Gynäkologie und Geburtshilfe, Klinikum Offenbach, Germany.
Christian
C
Jackisch
Breast cancer, metastatic; Dual inhibition; HER2-positive; Pertuzumab; Trastuzumab