(1) Perez EA (2) Barrios C (3) Eiermann W (4) Toi M (5) Im YH (6) Conte P (7) Martin M (8) Pienkowski T (9) Pivot X (10) Burris H 3rd (11) Petersen JA (12) Stanzel S (13) Strasak A (14) Patre M (15) Ellis P

Journal of clinical oncology Clinical Oncology

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.

Author Info: (1) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South

Author Info: (1) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (2) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (3) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (4) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (5) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (6) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (7) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (8) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (9) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (10) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (11) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (12) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (13) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (14) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom. (15) Edith A. Perez, Mayo Clinic, Jacksonville, FL; Howard Burris III, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Jennifer A. Petersen, Genentech, South San Francisco, CA; Carlos Barrios, Pontificia Universidade Catolica do Rio Grande do Sul School of Medicine, Porto Alegre, Brazil; Wolfgang Eiermann, Interdisciplinary Oncology Center, Munich, Germany; Masakazu Toi, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Young-Hyuck Im, Samsung Medical Centre, Seoul, Korea; Pierfranco Conte, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Miguel Martin, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; Xavier Pivot, University Hospital Jean Minjoz, Besancon, France; Sven Stanzel, Alexander Strasak, Monika Patre, F. Hoffmann-La Roche, Basel, Switzerland; and Paul Ellis, Guys Hospital and Sarah Cannon Research Institute, London, United Kingdom.

Citation: J Clin Oncol 2017 Jan 10 35:141-148. Epub 11/07/2016

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/28056202

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