Targeted Treatment of Metastatic Triple-Negative Breast Cancer: A Systematic Review

INTRODUCTION: Triple-negative breast cancer (TNBC) is a subgroup of breast cancer characterized by the absence of estrogen and the human epidermal 2 receptor and also a lack of targeted therapy options. Chemotherapy has so far been the only approved treatment option, and patients with metastatic cancer have a dismal prognosis with a median overall survival (OS) of approximately 14 months. Identification of druggable targets for metastatic TNBC is therefore of special interest.

METHODS: A systematic search was performed, to review the existing evidence on targeted therapies in metastatic TNBC.

RESULTS: A total of 37 phase 2/3 studies were identified, evaluating 29 different targeted agents. In this review, results on progression free survival (PFS) and OS are presented.

CONCLUSION: In most of the studies included, no improvement was observed for neither PFS nor OS; however, a few studies did show improvement with targeted agents and have led to new treatment options in subgroups of patients. The antibody drug conjugate, sacituzumab govitecan, demonstrated superior PFS and OS in comparison to chemotherapy. Immunotherapy with checkpoint inhibitors such as atezolizumab and pembrolizumab is now recommended as a first-line treatment option for patients with expression a PD-L1 positive tumor. Finally, the poly adenosine diphosphate-ribose polymerase (PARP) inhibitors talazoparib and olaparib are recommended, as first-line treatment options in patients with metastatic breast cancer and a germline BRCA mutation, but an immune checkpoint inhibitor should be considered for the subset of these patients who are PD-L1 positive.