Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer

Sara A. Hurvitz, Luc Dirix, Judit Kocsis, Giulia V. Bianchi, Janice Lu, Jeferson Vinholes, Ellie Guardino, Chunyan Song, Barbara Tong, Vivian Ng, Yu Waye Chu, Edith A. Perez

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Abstract

Purpose: Trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab via a stable thioether linker, has shown clinical activity in single-arm studies enrolling patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) whose disease had progressed on HER2-targeted therapy in the metastatic setting Patients and Methods: Patients (N = 137) with HER2-positive MBC or recurrent locally advanced breast cancer were randomly assigned to trastuzumab plus docetaxel (HT; n = 70) or T-DM1 (n = 67) as first-line treatment until disease progression or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (PFS) and safety. Key secondary end points included overall survival (OS), objective response rate (ORR), duration of objective response, clinical benefit rate, and quality of life. Results: Median PFS was 9.2 months with HT and 14.2 months with T-DM1 (hazard ratio, 0.59; 95% CI, 0.36 to 0.97); median follow-up was approximately 14 months in both arms. ORR was 58.0% (95% CI, 45.5% to 69.2%) with HT and 64.2% (95% CI, 51.8% to 74.8%) with T-DM1. T-DM1 had a favorable safety profile versus HT, with fewer grade ≥ 3 adverse events (AEs; 46.4% v 90.9%), AEs leading to treatment discontinuations (7.2% v 40.9%), and serious AEs (20.3% v 25.8%). Preliminary OS results were similar between treatment arms; median follow-up was approximately 23 months in both arms. Conclusion: In this randomized phase II study, first-line treatment with T-DM1 for patients with HER2-positive MBC provided a significant improvement in PFS, with a favorable safety profile, versus HT.

Original languageEnglish (US)
Pages (from-to)1157-1163
Number of pages7
JournalJournal of Clinical Oncology
Volume31
Issue number9
DOIs
StatePublished - Mar 20 2013

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docetaxel
Breast Neoplasms
Disease-Free Survival
Safety
Therapeutics
Survival
Cytotoxins
Sulfides
Disease Progression
Quality of Life
Research Personnel
ado-trastuzumab emtansine
human ERBB2 protein
Trastuzumab
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. / Hurvitz, Sara A.; Dirix, Luc; Kocsis, Judit; Bianchi, Giulia V.; Lu, Janice; Vinholes, Jeferson; Guardino, Ellie; Song, Chunyan; Tong, Barbara; Ng, Vivian; Chu, Yu Waye; Perez, Edith A.

In: Journal of Clinical Oncology, Vol. 31, No. 9, 20.03.2013, p. 1157-1163.

Research output: Contribution to journalArticle

Hurvitz, SA, Dirix, L, Kocsis, J, Bianchi, GV, Lu, J, Vinholes, J, Guardino, E, Song, C, Tong, B, Ng, V, Chu, YW & Perez, EA 2013, 'Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer', Journal of Clinical Oncology, vol. 31, no. 9, pp. 1157-1163. https://doi.org/10.1200/JCO.2012.44.9694
Hurvitz, Sara A. ; Dirix, Luc ; Kocsis, Judit ; Bianchi, Giulia V. ; Lu, Janice ; Vinholes, Jeferson ; Guardino, Ellie ; Song, Chunyan ; Tong, Barbara ; Ng, Vivian ; Chu, Yu Waye ; Perez, Edith A. / Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 9. pp. 1157-1163.
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abstract = "Purpose: Trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab via a stable thioether linker, has shown clinical activity in single-arm studies enrolling patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) whose disease had progressed on HER2-targeted therapy in the metastatic setting Patients and Methods: Patients (N = 137) with HER2-positive MBC or recurrent locally advanced breast cancer were randomly assigned to trastuzumab plus docetaxel (HT; n = 70) or T-DM1 (n = 67) as first-line treatment until disease progression or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (PFS) and safety. Key secondary end points included overall survival (OS), objective response rate (ORR), duration of objective response, clinical benefit rate, and quality of life. Results: Median PFS was 9.2 months with HT and 14.2 months with T-DM1 (hazard ratio, 0.59; 95{\%} CI, 0.36 to 0.97); median follow-up was approximately 14 months in both arms. ORR was 58.0{\%} (95{\%} CI, 45.5{\%} to 69.2{\%}) with HT and 64.2{\%} (95{\%} CI, 51.8{\%} to 74.8{\%}) with T-DM1. T-DM1 had a favorable safety profile versus HT, with fewer grade ≥ 3 adverse events (AEs; 46.4{\%} v 90.9{\%}), AEs leading to treatment discontinuations (7.2{\%} v 40.9{\%}), and serious AEs (20.3{\%} v 25.8{\%}). Preliminary OS results were similar between treatment arms; median follow-up was approximately 23 months in both arms. Conclusion: In this randomized phase II study, first-line treatment with T-DM1 for patients with HER2-positive MBC provided a significant improvement in PFS, with a favorable safety profile, versus HT.",
author = "Hurvitz, {Sara A.} and Luc Dirix and Judit Kocsis and Bianchi, {Giulia V.} and Janice Lu and Jeferson Vinholes and Ellie Guardino and Chunyan Song and Barbara Tong and Vivian Ng and Chu, {Yu Waye} and Perez, {Edith A.}",
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T1 - Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer

AU - Hurvitz, Sara A.

AU - Dirix, Luc

AU - Kocsis, Judit

AU - Bianchi, Giulia V.

AU - Lu, Janice

AU - Vinholes, Jeferson

AU - Guardino, Ellie

AU - Song, Chunyan

AU - Tong, Barbara

AU - Ng, Vivian

AU - Chu, Yu Waye

AU - Perez, Edith A.

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N2 - Purpose: Trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab via a stable thioether linker, has shown clinical activity in single-arm studies enrolling patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) whose disease had progressed on HER2-targeted therapy in the metastatic setting Patients and Methods: Patients (N = 137) with HER2-positive MBC or recurrent locally advanced breast cancer were randomly assigned to trastuzumab plus docetaxel (HT; n = 70) or T-DM1 (n = 67) as first-line treatment until disease progression or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (PFS) and safety. Key secondary end points included overall survival (OS), objective response rate (ORR), duration of objective response, clinical benefit rate, and quality of life. Results: Median PFS was 9.2 months with HT and 14.2 months with T-DM1 (hazard ratio, 0.59; 95% CI, 0.36 to 0.97); median follow-up was approximately 14 months in both arms. ORR was 58.0% (95% CI, 45.5% to 69.2%) with HT and 64.2% (95% CI, 51.8% to 74.8%) with T-DM1. T-DM1 had a favorable safety profile versus HT, with fewer grade ≥ 3 adverse events (AEs; 46.4% v 90.9%), AEs leading to treatment discontinuations (7.2% v 40.9%), and serious AEs (20.3% v 25.8%). Preliminary OS results were similar between treatment arms; median follow-up was approximately 23 months in both arms. Conclusion: In this randomized phase II study, first-line treatment with T-DM1 for patients with HER2-positive MBC provided a significant improvement in PFS, with a favorable safety profile, versus HT.

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