Fiche publication
Date publication
janvier 2017
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr PIVOT Xavier
Tous les auteurs :
Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P
Lien Pubmed
Résumé
Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast cancer.
Mots clés
Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, administration & dosage, Antineoplastic Combined Chemotherapy Protocols, administration & dosage, Breast Neoplasms, chemistry, Bridged-Ring Compounds, administration & dosage, Drug Tolerance, Female, Humans, Maytansine, administration & dosage, Middle Aged, Quality of Life, Random Allocation, Receptor, ErbB-2, analysis, Taxoids, administration & dosage, Trastuzumab, administration & dosage
Référence
J. Clin. Oncol.. 2017 Jan;35(2):141-148
