Pertuzumab and trastuzumab: the rationale way to synergy.
It has now been 15 years since the HER2-targeted monoclonal antibody trastuzumab was introduced in clinical and revolutionized the treatment of HER2-positive breast cancer patients. Despite this achievement, most patients with HER2-positive metastatic breast cancer still show progression of their disease, highlighting the need for new therapies. The continuous interest in novel targeted agents led to the development of pertuzumab, the first in a new class of agents, the HER dimerization inhibitors. Pertuzumab is a novel recombinant humanized antibody directed against extracellular domain II of HER2 protein that is required for the heterodimerization of HER2 with other HER receptors, leading to the activation of downstream signalling pathways. Pertuzumab combined with trastuzumab plus docetaxel was approved for the first-line treatment of patients with HER2-positive metastatic breast cancer and is currently used as a standard of care in this indication. In the neoadjuvant setting, the drug was granted FDA-accelerated approval in 2013. Pertuzumab is also being evaluated in the adjuvant setting. The potential of pertuzumab relies in the dual complete blockade of the HER2/3 axis when administered with trastuzumab. This paper synthetises preclinical and clinical data on pertuzumab and highlights the mechanisms underlying the synergistic activity of the combination pertuzumab-trastuzumab which are essentially due to their complementary mode of action.
Medical Oncology Department, APREC (Alliance Pour la Recherche En Cancérologie), Tenon Hospital (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), rue de la Chine, 75020 Paris, France, Medical Oncology Department, Tenon Hospital, Paris , France.
Sandrine
S
Richard
Medical Oncology Department, APREC (Alliance Pour la Recherche En Cancérologie), Tenon Hospital (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), rue de la Chine, 75020 Paris, France, Medical Oncology Department, Tenon Hospital, Paris , France.
Frédéric
F
Selle
Medical Oncology Department, APREC (Alliance Pour la Recherche En Cancérologie), Tenon Hospital (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), rue de la Chine, 75020 Paris, France, Medical Oncology Department, Tenon Hospital, Paris , France.|Institut Universitaire de Cancérologie Université Pierre et Marie Curie (IUC-UPMC Univ Paris 06), Sorbonne Universités, 4 place Jussieu, 75005 Paris, France, Université Curie Paris 6, Institut Universitaire de Cancérologie, Université Pierre et Marie Curie, Paris , France.
Jean-Pierre
JP
Lotz
Medical Oncology Department, APREC (Alliance Pour la Recherche En Cancérologie), Tenon Hospital (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), rue de la Chine, 75020 Paris, France, Medical Oncology Department, Tenon Hospital, Paris , France.
Ahmed
A
Khalil
Medical Oncology Department, APREC (Alliance Pour la Recherche En Cancérologie), Tenon Hospital (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), rue de la Chine, 75020 Paris, France, Medical Oncology Department, Tenon Hospital, Paris , France.|Institut Universitaire de Cancérologie Université Pierre et Marie Curie (IUC-UPMC Univ Paris 06), Sorbonne Universités, 4 place Jussieu, 75005 Paris, France, Université Curie Paris 6, Institut Universitaire de Cancérologie, Université Pierre et Marie Curie, Paris , France.
Joseph
J
Gligorov
Medical Oncology Department, APREC (Alliance Pour la Recherche En Cancérologie), Tenon Hospital (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), rue de la Chine, 75020 Paris, France, Medical Oncology Department, Tenon Hospital, Paris , France.
Daniele G
DG
Soares
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000627:therapeutic use; D000068878:Trastuzumab / Q000627:therapeutic use*
D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C485206:pertuzumab