Key Updates in Metastatic HER2+ Breast Cancer
Sara M. Tolaney, MD, MPH, reviews key clinical trial data recently updated in the metastatic HER2+ breast cancer treatment space.
This is a synopsis of an OncView series featuring Sara M. Tolaney, MD, MPH, of Dana-Farber Cancer Institute.
Sara M. Tolaney, MD, MPH, Chief of Breast Oncology at Dana-Farber Cancer Institute, discussed major advances in metastatic HER2-positive breast cancer, including the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) and the HER2-specific tyrosine kinase inhibitor (TKI) tucatinib.
The DESTINY-Breast03 trial showed T-DXd tripled progression-free survival (PFS) and improved overall survival compared to trastuzumab emtansine (T-DM1) in previously treated HER2-positive metastatic breast cancer. With a 28-month PFS, T-DXd exceeded the 18-month PFS seen with first-line standard-of-care trastuzumab, pertuzumab, and a taxane (THP). Ongoing trials are testing T-DXd in earlier lines, including first-line in DESTINY-Breast09. If positive, T-DXd may replace THP upfront.
The HER2CLIMB trial added tucatinib to capecitabine and trastuzumab, showing improvements in PFS and overall survival over capecitabine/trastuzumab alone, including in the 50% of patients with treated or active brain metastases. This is the first HER2-targeted therapy to show survival benefit in brain metastases. Tucatinib’s label allows second-line use, sparing some patients upfront brain radiation.
While studies suggest T-DXd has intracranial activity, direct comparisons are lacking as most T-DXd trials excluded active brain metastases. Additional results are expected from trials like DESTINY-Breast12 specifically evaluating T-DXd in this population.
Both tucatinib- and T-DXd-containing regimens have shown substantial efficacy in advanced HER2-positive disease, though optimal sequences are still being defined. Ongoing trials continue to evaluate combinations and positioning to maximize the impact of these promising new targeted therapies.
In summary, T-DXd and tucatinib represent major recent advances providing more effective and brain-penetrant options for patients with previously poor prognosis metastatic HER2-positive breast cancer.
*Video synopsis is AI-generated and reviewed by Cancer Network editorial staff.
