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Conjugate drug extends survival in patients with advanced HER2-positive breast cancer

  • Ian Krop, MD, PhD

    Patients with metastatic, HER2-positive breast cancer who received a combination antibody/chemotherapy drug in a phase 3 clinical trial survived longer, on average, than patients receiving other treatments. Researchers from Dana-Farber Cancer Institute reported the findings at the 2015 San Antonio Breast Cancer Symposium.

    The TH3RESA trial, which enrolled more than 600 participants in the U.S. and overseas, compared survival times in patients randomized to treatment with the conjugate drug trastuzumab emtansine (T-DM1) to those randomized to treatment of their physician’s choice. All patients had metastatic breast cancer that tested positive for the human epidermal growth factor receptor 2 (HER2) protein – a feature in about 20 percent of all breast cancers – and had previously been treated with chemotherapy as well as the HER2-targeted drugs trastuzumab and lapatinib.

    The investigators found that those in the T-DM1 group lived a median of 22.7 months vs. 15.8 months for those in the treatment of physician’s choice group – a 44 percent improvement. (The treatment of physician’s choice consisted either of drug regimens that targeted HER2 or single-agent chemotherapy.) The survival benefit associated with T-DM1 was consistent across all patient subgroups, regardless of age, degree of metastasis, number of prior treatments, and type of treatment of physician’s choice.

    The incidence of severe side effects deemed severe or greater was also lower in the T-DM1 group – 40 percent, compared to 47.3 percent for those in the treatment of physician’s choice group. 

    T-DM1 combines trastuzumab, an antibody that latches onto the HER2 protein and blocks it from receiving growth signals, and emtansine, a potent chemotherapy drug that disrupts the way cells grow. By attaching the emtansine to trastuzumab, T-DM1 delivers the emtansine directly to the HER2-positive cancer cells. This essentially makes emtansine into a targeted drug that is highly effective at killing HER2+ cancer cells, but largely avoids damaging normal cells.

    “This is an important trial because it demonstrates that even in patients whose cancer has progressed on multiple other HER2-targeted therapies, treatment with T-DM1 substantially extends patient survival compared to other drugs,” said the study’s senior author, Ian Krop, MD, PhD, Senior Physician in the Susan F. Smith Center for Women’s Cancers at Dana-Farber. “In addition, T-DM1 causes fewer serious side effects than other treatments. Based on this study and others, T-DM1 should be considered the standard of care for patients whose cancer has progressed on a HER2-targeted treatment.”

    The first author of the study is Hans Wildiers of University Hospitals Leuven, Leuven, Belgium.  Co-authors are Sung-Bae Kim of Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Antonio Gonzalez-Martin, of Centro Oncológico MD Anderson International España, Madrid, Spain; Patricia M. LoRusso, of Yale Cancer Center; Jean-Marc Ferrero of Centre Antoine Lacassagne, Nice, France; and Ron Yu and Melanie Smitt of Genentech, Inc.

Posted on December 11, 2015

  • Ian E. Krop, MD, PhD
  • Breast Cancer
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