Advanced/Metastatic HER2+ Treatment Options and Rationale

Adam M. Brufsky, MD, PhD


January 31, 2023

The development of HER2-targeted therapies has significantly enhanced the outcomes for patients with HER2+ breast cancer, and mounting evidence continues to refine systemic strategies in advanced/metastatic disease.

Dr Adam Brufsky, of the University of Pittsburgh School of Medicine, shares expanding treatment options for second line and later line therapy. He begins with the DESTINY-Breast03 trial, which demonstrated the use of trastuzumab deruxtecan (T-DXd) as a second-line therapy for HER2+ advanced breast cancer. T-DXd yielded superior overall survival (OS) and progression-free survival (PFS) rates in patients with HER2+ metastatic breast cancer. The agent also showed a benefit in central nervous system (CNS) metastases.

In addition, he reports, the use of the combination of neratinib and capecitabine, specifically for HER2+ patients with brain metastases (BM) at baseline, has shown gains in PFS and CNS metastases, as demonstrated by the NALA trial.

Finally, Dr Brufsky discusses the HER2CLIMB trial, which examines the use of tucatinib in combination with trastuzumab and capecitabine for patients with previously treated metastatic HER2+ breast cancer, including those with BM. Results showed significant improvement in OS and PFS. Tyrosine kinase inhibitors such as neratinib and tucatinib are now a standard of treatment for this vulnerable population.


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