Key Updates in Metastatic HER2+ Breast Cancer

EP: 1.The Overall Breast Cancer Landscape

EP: 2.Recent Updates for Biomarker Testing in Breast Cancer

EP: 3.The Role of Ki-67 and ctDNA as Prognostic or Predictive Markers in Breast Cancer

EP: 4.CDK4/6 & PARP Inhibitors for Early-Stage Breast Cancer

EP: 5.Evolving Treatment Landscape for HER2+ Breast Cancer

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EP: 6.Key Updates in Metastatic HER2+ Breast Cancer

EP: 7.Treatment Landscape for Triple-Negative Breast Cancer

EP: 8.Emerging Therapies and Ongoing Trials in Breast Cancer

EP: 9.Clinical Pearls for the Treatment of Breast Cancer

EP: 10.Personalized Treatment Sequencing Is a New Way of Thinking in Breast Cancer

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.