What is the role of ado-trastuzumab (Kadcyla) in the treatment of HER2-positive breast cancer?

Updated: May 14, 2019
  • Author: Maurie Markman, MD, MS; Chief Editor: Karl S Roth, MD  more...
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Only 1 in 3 HER2-positive metastatic breast cancer patients respond to single-agent trastuzumab, and most, if not all, eventually develop resistance. To overcome resistance, trastuzumab has been modified using a covalent linker to attach DM1, a derivative of the microtubule destabilizer maytansine. Ado-trastuzumab (Kadcyla) was approved as a single agent for treatment of HER2-positive, metastatic breast cancer in patients who have already undergone unsuccessful treatment with trastuzumab and a taxane, either separately or in combination.

By exploiting trastuzumab to target the cytotoxic activity of DM1 to HER2-overexpressing cells, ado-trastuzumab offers a novel mechanism for overcoming trastuzumab resistance. A phase I trial of every-3-week ado-trastuzumab demonstrated a clinical benefit rate of 53% in metastatic breast cancer patients that had progressed on previous trastuzumab. Additionally, preliminary results from a phase II trial reported an objective response rate of 43%. [24] Approval was based on results from EMILIA, an international phase III study comparing ado-trastuzumab to lapatinib plus capecitabine (n=991). The study showed a significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine. [18]

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