Trastuzumab Emtansine Shows Promise for HER2+ Metastatic Breast Cancer

Strategic Insights -

Researchers in the United Kingdom are developing trastuzumab emtansine, an antibody-drug conjugate, for the treatment of HER2+ metastatic breast cancer. Studies have shown that trastuzumab emtansine is effective in breast cancer cell lines resistant to trastuzumab and demonstrated complete tumor regression in SCID mice bearing KPL4 breast cancer xenografts. Clinical trials have also reported efficacy in patients with HER2+ metastatic breast cancer who had progressed on previous chemotherapy regimens or with trastuzumab therapy.

Key Takeaways:

  • Trastuzumab emtansine is a tumor-activated prodrug resulting from the conjugation of trastuzumab and DM1, a cytotoxic and antimitotic maytansine derivative.
  • The maytansinoids bind microtubules in a manner similar to vinca alkaloids but have been recognized to be 20-to 100-fold more potent at blocking mitosis.
  • By conjugating DM1 with trastuzumab, the delivery of the cytotoxic agent to target cells is more specific and reduces safety concerns.
  • Trastuzumab emtansine has been shown to be effective in preclinical studies, including complete tumor regression in SCID mice bearing KPL4 breast cancer xenografts.
  • Clinical trials have reported efficacy in patients with HER2+ metastatic breast cancer who had progressed on previous chemotherapy regimens or with trastuzumab therapy.
  • Trastuzumab emtansine potentiates the effect of various chemotherapeutic agents, including carboplatin, 5-fluorouracil, and docetaxel, and other treatments.
  • Researchers have concluded that trastuzumab emtansine offers an exciting new option for the treatment of patients with refractory, metastatic breast cancer.

Statistics:

  • Trastuzumab emtansine has been shown to be 20-to 100-fold more potent than vinca alkaloids at blocking mitosis.
  • Preclinical studies have reported complete tumor regression in SCID mice bearing KPL4 breast cancer xenografts treated with trastuzumab emtansine.
  • Clinical trials have reported efficacy in patients with HER2+ metastatic breast cancer who had progressed on previous chemotherapy regimens or with trastuzumab therapy.

Sources:

  • Niculescu-Duvaz, I., et al. (2010) "Trastuzumab emtansine, an antibody-drug conjugate for the treatment of HER2+ metastatic breast cancer." Current Opinion In Molecular Therapeutics, 12(3), 350-360.
  • Biotech Week editors (2010) "Trastuzumab Emtansine Shows Promise for HER2+ Metastatic Breast Cancer." Biotech Week.