Abstract SP083: Treatment of HER2-positive metastatic breast cancer - advances and challenges

Abstract

Over the past two decades, there have been tremendous advances in treatment options for patients with HER2+ metastatic breast cancer (MBC). Median overall survival (OS) in control arm of the pivotal trastuzumab + chemotherapy study (Slamon et al, NEJM 2001) was 20.3 months. By contrast, median OS in the taxane/trastuzumab/pertuzumab arm of the CLEOPATRA trial was approximately 5 years, with an 8-year landmark OS of 37% (Wong et al, Oncologist 2019). Notably, OS improvements have also been demonstrated in the pivotal trials of ado-trastuzumab emtansine, tucatinib/capecitabine/trastuzumab, and trastuzumab deruxtecan in pre-treated patients with HER2+ MBC, such that we expect that median OS will only continue to lengthen. Indeed, with current therapies, a subset of patients can survive a decade or longer. Despite these improvements, there is still much progress to be made. First, the problem of brain metastases continues to contribute substantial morbidity and mortality in at least half of patients. While there have been advances in local therapy for brain metastases, breakthroughs in systemic therapy and prevention strategies ultimately will be needed to truly tackle this problem. Second, drug resistance nearly always appears over time, yet our understanding of HER2-resistance remains woefully incomplete. Developing a deeper understanding of therapeutic resistance may uncover novel targets that allow for more effective and durable treatment. Finally, with multiple highly active drugs now available, is it now time to pivot to testing curative-intent approaches in HER2+ MBC, particularly in those patients who present with de novo stage IV disease. Citation Format: N Lin. Treatment of HER2-positive metastatic breast cancer - advances and challenges [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP083.