title: [Trastuzumab emtansine (Kadcyla(®)) approval in HER2-positive metastatic breast cancers].
abstract: HER2 (human epidermal growth factor receptor 2) is overexpressed in 15 to 20% of breast cancer. Anti-HER2 targeted therapies, notably trastuzumab, have transformed the natural history of this disease. Trastuzumab emtansine, consisting of trastuzumab coupled to a cytotoxic agent, emtansine (DM1), by a stable linker, has been approved in November 2013 by the European Medicine Agency. Trastuzumab emtansine targets and inhibits HER2 signaling, but also allows emtansine to be directly delivered inside HER2-positive cancer cells. It is indicated as single-agent in taxane and trastuzumab-pretreated HER2-positive breast cancer patients with metastatic and locally recurrent unresecable disease or relapsing within 6 months of the end of adjuvant therapy. This indication is based on the results of the EMILIA study, an open label phase III randomized trial comparing trastuzumab emtansine to lapatinib-capecitabine. The two primary endpoints were reached. The progression-free survival was 6.4 months in the lapatinib-capecitabine arm versus 9.6 months for the trastuzumab emtansine arm (HR=0.65; 95% CI=0.55-0.77, P<0.001). Overall survival at the second interim analysis was 25.1 months in the lapatinib-capecitabine arm versus 30.9 months in the trastuzumab emtansine arm (HR=0.68; 95% CI=0.55-0.85, P<0.001). Moreover, adverse events were more frequent in the lapatinib-capecitabine arm.
authors: Institut Paoli-Calmettes, oncologie médicale, 232, boulevard Ste-Marguerite, 13009 Marseille, France; Inserm U1068-CNRS U7258, Aix-Marseille université, centre de recherche en cancérologie de Marseille, 13009 Marseille, France.
authors: Mathilde
authors: M
authors: Guerin
authors: Institut Paoli-Calmettes, oncologie médicale, 232, boulevard Ste-Marguerite, 13009 Marseille, France; Inserm U1068-CNRS U7258, Aix-Marseille université, centre de recherche en cancérologie de Marseille, 13009 Marseille, France; Aix-Marseille université, 13284 Marseille cedex 07, France.
authors: Renaud
authors: R
authors: Sabatier
authors: Institut Paoli-Calmettes, oncologie médicale, 232, boulevard Ste-Marguerite, 13009 Marseille, France; Inserm U1068-CNRS U7258, Aix-Marseille université, centre de recherche en cancérologie de Marseille, 13009 Marseille, France; Aix-Marseille université, 13284 Marseille cedex 07, France. Electronic address: GONCALVESA@ipc.unicancer.fr.
authors: Anthony
authors: A
authors: Gonçalves
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017326:Clinical Trials, Phase III as Topic; D017277:Drug Approval; D005260:Female; D006801:Humans; D008453:Maytansine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009363:Neoplasm Proteins / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008453:Maytansine; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Cancer du sein métastatique; HER2; Metastatic breast cancers; Trastuzumab emtansine