title: The European Medicines Agency Review of Pertuzumab for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer: summary of the scientific assessment of the committee for medicinal products for human use.
abstract: Pertuzumab is a recombinant humanized monoclonal antibody that specifically targets the extracellular dimerization domain (subdomain II) of HER2. Based on the positive opinion from the European Medicines Agency (EMA) on March 4, 2013, a marketing authorization valid throughout the European Union (EU) was issued for pertuzumab (Perjeta) for use in combination with trastuzumab and docetaxel for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer who have not received previous anti-HER2 therapy or chemotherapy for their metastatic disease. The demonstration of clinical benefit for pertuzumab was based on a single, phase III, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel in previously untreated patients with locally advanced or metastatic HER2-positive breast cancer. In the primary analysis, median progression-free survival was 18.5 months in the pertuzumab group compared with 12.4 months in the placebo group (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.51-0.75; p < .0001). For the secondary endpoints, overall survival (HR: 0.66; 95% CI: 0.52-0.84; p = .0008) and objective response rate (80.2% vs. 69.3%) were also favored in the pertuzumab group. Toxicity was similar between groups except for higher incidence of diarrhea, rash, mucosal inflammation, dry skin, and neutropenia for pertuzumab compared with placebo. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (http://www.ema.europa.eu).
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands Hector.Boix@ema.europa.eu.
authors.forename: Hector
authors.initials: H
authors.lastname: Boix-Perales
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Jeanett
authors.initials: J
authors.lastname: Borregaard
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Kristina Bech
authors.initials: KB
authors.lastname: Jensen
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Jens
authors.initials: J
authors.lastname: Ersbøll
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Sara
authors.initials: S
authors.lastname: Galluzzo
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Rosa
authors.initials: R
authors.lastname: Giuliani
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ciceroni
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Daniela
authors.initials: D
authors.lastname: Melchiorri
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Tomas
authors.initials: T
authors.lastname: Salmonson
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Schellens
authors.affiliation: European Medicines Agency, London, United Kingdom; Danish Health and Medicines Authority, København, Denmark; Department of Physiology and Pharmacology, Università di Roma "La Sapienza," Rome, Italy; Agenzia Italiana del Farmaco, Rome, Italy; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Karolinska Institutet, Stockholm, Sweden; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pignatti
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D005062:European Union; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D016019:Survival Analysis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C485206:pertuzumab
keywords: Breast cancer; EMA; European Medicines Agency; Perjeta; Pertuzumab