Clinical development of antibody-drug conjugates in triple negative breast cancer: can we jump higher?

Introduction: Triple negative breast cancer (TNBC) is an aggressive BC subtype, associated with higher rates of relapse and shorter overall survival upon metastatic relapse. The advent of antibody-drug conjugates (ADC), able to deliver selectively potent chemotherapeutic agents, has demonstrated promising clinical activity, with the first approval of an ADC, i.e. Sacituzumab Govitecan, in the metastatic setting. This paperprovides the most recent data indicating the promise of this novel class of drugs, as potential tools to improve clinical outcomes of patients diagnosed with TNBC.

Areas Covered: Upon review of the main characteristics of TNBC, and those of ADCs, an overview of the data from clinical trials assessing ADCs in TNBC is provided, including those that led to the first approval of such a drug for patients with metastatic disease; furthermore, several other ADCs targeting different proteins (over)expressed by TNBC undergo clinical development. Combinations of ADCs with other targeted agents are discussed; the most pertinent considerations for improving the chances of successful clinical development of ADCs in TNBC are provided.

Expert Opinion: ADCs could further improve clinical outcomes of patients with TNBC, and successful development depends upon: i) successful triaging of patients with the right ADC, ii) technical optimization of ADCs to maximize the efficacy, while reducing toxicity, and iii) assess rationally chosen combinations with synergistic antitumor activity and acceptable safety profile.