Cancer Management and Research (Oct 2020)
Treatment Landscape for Patients with HER2-Positive Metastatic Breast Cancer: A Review on Emerging Treatment Options
Abstract
Simon Peter Gampenrieder,1,2 Vanessa Castagnaviz,1 Gabriel Rinnerthaler,1,2 Richard Greil1,2 1Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Paracelsus Medical University Salzburg, Salzburg, Austria; 2Cancer Cluster Salzburg, Salzburg, AustriaCorrespondence: Richard GreilIIIrd Medical Department, Paracelsus Medical University Salzburg, Müllner Hauptstraße 48, Salzburg 5020, AustriaTel +4357255-25801Fax +4357255-25999Email [email protected]: The prognosis of HER2-positive metastatic breast cancer (MBC) has radically changed in recent years and continues to improve due to the broad application of effective therapies like monoclonal antibodies and small molecules targeting HER2. Persistent dependency of tumor cells on the oncogene HER2, on one hand, as well as low expression levels in healthy tissue, on the other hand, make this protein an ideal target for anti-cancer therapy. New HER2 targeting strategies including targeted delivery of cytotoxic drugs via HER2 receptor have been developed. Recently, the US Food and Drug Administration (FDA) approved three new drugs for the treatment of HER2-positive MBC: the antibody–drug conjugate trastuzumab deruxtecan and the two tyrosine kinase inhibitors neratinib and tucatinib. Here, we summarize recent publications and developments of novel anti-HER2 therapies like monoclonal antibodies with improved properties compared to trastuzumab and bispecific antibodies, which bind two different HER-epitopes or bring T cells closer to tumor cells. Furthermore, novel antibody-drug conjugates and small molecules against HER2 are discussed. These developments coupled with new combination strategies (eg, with CDK4/6 inhibitors or immunotherapy) will change the treatment landscape for patients with HER2-positive MBC very soon and will hopefully further improve clinical outcomes.Keywords: margetuximab, bispecific antibodies, trastuzumab duocarmazine, trastuzumab deruxtecan, neratinib, tucatinib, immunotherapy, CDK4/6 inhibitors
