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Trastuzumab emtansine: A unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer

Clinical Cancer Research, ISSN: 1078-0432, Vol: 17, Issue: 20, Page: 6437-6447
2011
  • 404
    Citations
  • 0
    Usage
  • 384
    Captures
  • 5
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    404
    • Citation Indexes
      400
    • Patent Family Citations
      3
      • Patent Families
        3
    • Policy Citations
      1
      • Policy Citation
        1
  • Captures
    384
  • Mentions
    5
    • References
      4
      • Wikipedia
        4
    • News Mentions
      1
      • News
        1

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Paving the Way for Better Outcomes in HER2+ Early Breast Cancer Treatment

Optimizing treatment for early-stage human epidermal growth receptor 2 (HER2)-positive (HER2+) breast cancer (BC) requires a nuanced approach, integrating targeted therapies and personalized strategies to

Review Description

Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor (HER2)-targeted antibodydrug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine), in phase III development for HER2-positive cancer. Extensive analysis of T-DM1 in preclinical studies has shown that T-DM1 combines the distinct mechanisms of action of both DM1 and trastuzumab, and has antitumor activity in trastuzumab- and lapatinib-refractory experimental models. Clinically, T-DM1 has a consistent pharmacokinetics profile and minimal systemic exposure to free DM1, with no evidence of DM1 accumulation following repeated T-DM1 doses. Although a few covariates were shown to affect interindividual variability in T-DM1 exposure and clearance in population-pharmacokinetics analyses, the magnitude of their effect on T-DM1 exposure was not clinically relevant. Phase I and phase II clinical trials of T-DM1 as a single agent and in combination with paclitaxel, docetaxel, and pertuzumab have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. Two randomized phase III trials of T-DM1 are recruiting patients: EMILIA (NCT00829166) is evaluating T-DM1 compared with lapatinib plus capecitabine, andMARIANNE(NCT01120184) is evaluating T-DM1 plus placebo versus T-DM1 plus pertuzumab versus trastuzumab plus a taxane. Additional combinations of T-DM1 (for example, with GDC-0941) and additional disease settings (early-stage HER2-positive breast cancer) are also under investigation. Data from the phase III trials and other studies of T-DM1-containing agents are eagerly awaited. ©2011 AACR.

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