4.3 Review

Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in breast cancer therapeutics

Journal

EXPERT OPINION ON BIOLOGICAL THERAPY
Volume 21, Issue 7, Pages 945-962

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/14712598.2021.1936494

Keywords

Breast cancer; antibody-drug conjugate; immune checkpoint inhibitor; bystander effect; atezolizumab; pembrolizumab; sacituzumab govitecan; trastuzumab deruxtecan; trastuzumab emtansine; dual therapy

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Advanced breast cancer remains incurable, but there have been promising developments in the use of ADCs and ICIs for patients. Combining newer ADCs and ICIs for different subtypes of breast cancer shows potential synergy in improving treatment outcomes. The development of next-generation ADCs, rational combination strategies with ICIs, and the use of immune biomarkers could significantly enhance the outlook for patients with refractory aBC.
Introduction Advanced breast cancer (aBC) remains incurable and the quest for more effective systemic anticancer agents continues. Promising results have led to the FDA approval of three antibody-drug conjugates (ADCs) and two immune checkpoint inhibitors (ICIs) to date for patients with aBC. Areas covered With the anticipated emergence of newer ADCs and ICIs for patients with several subtypes of breast cancer, and given their potential synergy, their use in combination is of clinical interest. In this article, we review the use of ADCs and ICIs in patients with breast cancer, assess the scientific rationale for their combination, and provide an overview of ongoing trials and some early efficacy and safety results of such dual therapy. Expert Opinion Improvement in the medicinal chemistry of next-generation ADCs, their rational combination with ICIs and other agents, and the development of multiparametric immune biomarkers could help to significantly improve the outlook for patients with refractory aBC.

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