Breast Cancer Treatment and Antibody Drug Conjugates: Beyond T-DM1

Abstract

Antibody–drug conjugates (ADCs) are a new class of anticancer agents that combine cytotoxic agents attached by a linker to a monoclonal antibody. These engineered drugs can selectively deliver a cytotoxic payload to targeted cancer cells and the local microenvironment (bystander effect), thereby increasing activity and reducing off-target toxicity. The association of ADCs with other anti-cancer therapies is therefore promising. Trastuzumab-emtansine was the first approved ADC in breast cancer (BC), specifically for the management of human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. New ADCs are in development in BC. Some have shown meaningful clinical benefit and have been recently approved, such as trastuzumab deruxtecan in HER2-positive trastuzumab emtansine (T-DM1) pretreated BC and Trop-2 guided sacituzumab govitecan in triple-negative BC. Trastuzumab deruxtecan also has potential clinical activity in HER2-low BC thanks to a bystander effect. In this article, we review the ADCs under development in advanced BC.