Future directions on Antibody-Drug Conjugates in HER-2 negative Breast Cancer: a Comprehensive Review of New Agents

Abstract

Background: Breast Cancer is the most frequent malignancy in women with a rising incidence. Antibody-drug conjugates targeting HER2 and TROP-2 are new tools already effective against breast cancer but ADCs targeting new transmembrane receptors are necessary to overcome the dependence on HER-2 pathway. New trials are emerging fast as new ADCs are under investigation. Methods: We reviewed ClinicalTrials.gov and Pubmed for early clinical trials on new ADCs in clinical development for HER-2 negative breast cancer. Results: Trials testing 12 new molecules were found. Pre-clinical studies, safety and results in phase I/II trials published of each new molecule were reviewed and described briefly. Side effects regarding ADCs with maytansine derivatives (DM1/4) or auristatins (MMAE/MMAF) payloads were described. Conclusion: ADCs represent a practice-changing therapy for cancer treatment. New compounds against several new targets are expected to become part of clinical practice in the near future.