Relationship between HER2 expression and efficacy with first-line trastuzumab emtansine compared with trastuzumab plus docetaxel in TDM4450g

A randomized phase II study of patients with previously untreated HER2-positive metastatic breast cancer

Edith A. Perez, Sara A. Hurvitz, Lukas C. Amler, Kirsten E. Mundt, Vivian Ng, Ellie Guardino, Luca Gianni

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Abstract

Introduction: The purpose of this study was to retrospectively explore the relationship between human epidermal growth factor receptor 2 (HER2) messenger RNA (mRNA) expression and efficacy in patients receiving trastuzumab plus docetaxel (HT) or trastuzumab emtansine (T-DM1).Methods: Patients with HER2-positive, locally advanced or metastatic breast cancer (MBC) were randomly assigned to HT (n = 70) or T-DM1 (n = 67). HER2 status was assessed locally using immunohistochemistry or fluorescence in situ hybridization and confirmed retrospectively by central testing. HER2 mRNA expression was assessed using quantitative reverse transcriptase polymerase chain reaction.Results: HER2 mRNA levels were obtained for 116/137 patients (HT = 61; T-DM1 = 55). Median pretreatment HER2 mRNA was 8.9. The risk of disease progression in the overall population was lower with T-DM1 than with HT (hazard ratio (HR) = 0.59; 95% confidence interval (CI) 0.36 to 0.97). This effect was more pronounced in patients with HER2 mRNA ≥ median (HR = 0.39; 95% CI 0.18 to 0.85) versus <median (HR = 0.85; 95% CI 0.44 to 1.67). In the T-DM1 arm, median progression-free survival (PFS) was not reached in patients with HER2 mRNA ≥ median and was 10.6 months in patients with HER2 mRNA <median. In the HT arm, PFS was 8.8 versus 9.8 months in patients with HER2 mRNA ≥ median versus <median, respectively. The effect of HER2 mRNA expression on objective response rates was less pronounced.Conclusions: This exploratory analysis suggests that while overall, patients with HER2-positive MBC show improved PFS with T-DM1 relative to HT, the effect is enhanced in patients with tumor HER2 mRNA ≥ median. Trial registration: ClinicalTrials.gov NCT00679341.

Original languageEnglish
Article numberR50
JournalBreast Cancer Research
Volume16
Issue number3
DOIs
Publication statusPublished - May 23 2014

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docetaxel
Breast Neoplasms
Messenger RNA
Disease-Free Survival
Confidence Intervals
human ERBB2 protein
Trastuzumab
ado-trastuzumab emtansine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Relationship between HER2 expression and efficacy with first-line trastuzumab emtansine compared with trastuzumab plus docetaxel in TDM4450g : A randomized phase II study of patients with previously untreated HER2-positive metastatic breast cancer. / Perez, Edith A.; Hurvitz, Sara A.; Amler, Lukas C.; Mundt, Kirsten E.; Ng, Vivian; Guardino, Ellie; Gianni, Luca.

In: Breast Cancer Research, Vol. 16, No. 3, R50, 23.05.2014.

Research output: Contribution to journalArticle

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