Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: Primary results from the phase III MARIANNE study

Edith A. Perez, Carlos Barrios, Wolfgang Eiermann, Masakazu Toi, Young Hyuck Im, Pierfranco Conte, Miguel Martin, Tadeusz Pienkowski, Xavier Pivot, Howard Burris, Jennifer A. Petersen, Sven Stanze, Alexander Strasak, Monika Patre, Paul Ellis

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number2
DOIs
StatePublished - Jan 10 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Perez, E. A., Barrios, C., Eiermann, W., Toi, M., Im, Y. H., Conte, P., Martin, M., Pienkowski, T., Pivot, X., Burris, H., Petersen, J. A., Stanze, S., Strasak, A., Patre, M., & Ellis, P. (2017). Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: Primary results from the phase III MARIANNE study. Journal of Clinical Oncology, 35(2), 141-148. https://doi.org/10.1200/JCO.2016.67.4887