ESMO E-Learning: Present and Emerging Treatment Options in HER2-positive Metastatic Breast Cancer

In recent decades, the human epidermal growth factor receptor 2 (HER2) has become a major therapeutic target in patients with breast cancer. Trastuzumab and other HER2 directed agents have been developed for treatment use, creating an array of therapeutic options for patients with breast cancer. This E-learning module focuses on present and emerging treatment options in patients with HER2-positive metastatic breast cancer.  

The module starts by summarising evidence from the pivotal trials with chemotherapy plus trastuzumab for HER2-positive metastatic breast cancer, moving forward to the evidence from trials with dual HER2 inhibition, specifically the combination of trastuzumab and pertuzumab, explaining their synergistic activity. This is followed by antibody-drug conjugates, explaining mechanism of action, development, and clinical activity of trastuzumab-emtansine, followed by the results from the studies with trastuzumab deruxtecan, including a detailed explanation of the profile of its side effects.  

The chapter that follows, is devoted to the development of tyrosine kinase inhibitors (TKIs) and explanation of the results and side effects from the clinical trials with tucatinib, a third generation of HER2 TKI.     

The authors then illustrate the algorithms for practise according to the ESMO guidelines for the management of HER2-positive breast cancer, positioning the treatment available in first-, second, third-line and beyond.  

The topics elaborated further cover fields such as HER2 targeted treatment plus endocrine therapy in luminal B/HER2-positive metastatic breast cancer, optimising treatment in elderly and frail patients in terms of dual inhibition plus metronomic chemotherapy, HER2 targeting in population of patients with brain metastases, and the cases with isolated brain progression.  

Furthermore, the authors elaborate trastuzumab in multiple lines, vertical dual blockade with combining trastuzumab and TKIs, and summarise evidence in terms of further treatment options, such as neratinib, pyrotinib, margetuximab, trastuzumab duocarmazine, and combining CDK inhibitor and HER2-directed therapy, thus providing the audience with a comprehensive overview and very clear messages.