title: Pharmacokinetics, pharmacodynamics and clinical efficacy of pertuzumab in breast cancer therapy.
abstract: BACKGROUND
  Pertuzumab is a recombinant, humanized monoclonal antibody that binds to the dimerization domain of human epidermal growth factor receptor 2 (HER2), inhibiting the heterodimerization of HER2 with other HER receptors. It has shown synergy with trastuzumab in preclinical studies, and has led to a significant prolongation of progression-free and overall survival compared with placebo when added to trastuzumab and docetaxel for the first-line treatment of HER2-positive metastatic breast cancer (BC).
  
  
  METHODS
  The HER family of receptors and their pathways, pertuzumab pharmacodynamics and preclinical activity, results from the main clinical trials, new drug combinations being developed, and predictors of response are discussed.
  
  
  CONCLUSIONS
  Pertuzumab represents an important anti-HER2 agent that differs from, but is synergistic with, trastuzumab. It is already a standard of care in the first-line treatment of HER2-positive metastatic BC, and studies are ongoing to define its role in the adjuvant setting. It is now imperative to identify which tumors need dual HER2 targeting and to study the activity of pertuzumab in combination with other HER-targeted agents, including anti-HER1, -HER3 or -HER4, which could also prove useful in HER2-normal cancers. Potential competitors are anti-HER3 antibodies and bi- or tri-specific antibodies. Development in combination with phosphoinositide 3-kinase inhibitors or with anti PD-L1 is warranted.
authors: a 1 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology , Via P. Maroncelli 40, 47014 Meldola (FC), Italy +39 05 4373 9278 ; +39 05 4373 9249 ; andrea.rocca@irst.emr.it.
authors: Andrea
authors: A
authors: Rocca
authors: b 2 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials , Via P. Maroncelli 40, 47014 Meldola (FC), Italy.
authors: Daniele
authors: D
authors: Andreis
authors: a 1 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology , Via P. Maroncelli 40, 47014 Meldola (FC), Italy +39 05 4373 9278 ; +39 05 4373 9249 ; andrea.rocca@irst.emr.it.
authors: Anna
authors: A
authors: Fedeli
authors: a 1 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology , Via P. Maroncelli 40, 47014 Meldola (FC), Italy +39 05 4373 9278 ; +39 05 4373 9249 ; andrea.rocca@irst.emr.it.
authors: Roberta
authors: R
authors: Maltoni
authors: a 1 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology , Via P. Maroncelli 40, 47014 Meldola (FC), Italy +39 05 4373 9278 ; +39 05 4373 9249 ; andrea.rocca@irst.emr.it.
authors: Samanta
authors: S
authors: Sarti
authors: a 1 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology , Via P. Maroncelli 40, 47014 Meldola (FC), Italy +39 05 4373 9278 ; +39 05 4373 9249 ; andrea.rocca@irst.emr.it.
authors: Lorenzo
authors: L
authors: Cecconetto
authors: a 1 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology , Via P. Maroncelli 40, 47014 Meldola (FC), Italy +39 05 4373 9278 ; +39 05 4373 9249 ; andrea.rocca@irst.emr.it.
authors: Elisabetta
authors: E
authors: Pietri
authors: a 1 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology , Via P. Maroncelli 40, 47014 Meldola (FC), Italy +39 05 4373 9278 ; +39 05 4373 9249 ; andrea.rocca@irst.emr.it.
authors: Alessio
authors: A
authors: Schirone
authors: c 3 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Biosciences Laboratory , Via P. Maroncelli 40, 47014 Meldola (FC), Italy.
authors: Sara
authors: S
authors: Bravaccini
authors: b 2 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials , Via P. Maroncelli 40, 47014 Meldola (FC), Italy.
authors: Patrizia
authors: P
authors: Serra
authors: a 1 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology , Via P. Maroncelli 40, 47014 Meldola (FC), Italy +39 05 4373 9278 ; +39 05 4373 9249 ; andrea.rocca@irst.emr.it.
authors: Alberto
authors: A
authors: Farolfi
authors: a 1 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology , Via P. Maroncelli 40, 47014 Meldola (FC), Italy +39 05 4373 9278 ; +39 05 4373 9249 ; andrea.rocca@irst.emr.it.
authors: Dino
authors: D
authors: Amadori
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004357:Drug Synergism; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C485206:pertuzumab
keywords: HER2 dimerization inhibitors; HER2-positive breast cancer; HER2-targeted therapy; first-line metastatic therapy; neoadjuvant therapy; pertuzumab