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

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 34.8%), [corrected] 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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 31 Issue 9 Pg. 1157-63 (Mar 20 2013) ISSN: 1527-7755 [Electronic] United States
• PMID: 23382472 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Taxoids
• Maytansine
• Docetaxel
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab
• Ado-Trastuzumab Emtansine

Topics

• Ado-Trastuzumab Emtansine
• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, therapeutic use)
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Breast Neoplasms (chemistry, drug therapy, pathology)
• Docetaxel
• Female
• Humans
• Maytansine (administration & dosage, analogs & derivatives, therapeutic use)
• Middle Aged
• Neoplasm Metastasis
• Receptor, ErbB-2 (analysis)
• Taxoids (administration & dosage)
• Trastuzumab
• Treatment Outcome