Current treatment landscape and emerging therapies for metastatic triple-negative breast cancer.

Abstract

A lack of therapeutically targetable molecular alterations and its aggressive nature make triple-negative breast cancer (TNBC) a challenging disease. Chemotherapy is standard of care for most patients with metastatic disease, but median overall survival is less than 18 months. Unravelling the molecular underpinnings of TNBC revealed it to be a potentially highly immunogenic subtype within a more broadly immunologically inert cancer type, suggesting that it may respond to immunotherapy. An urgent need for new therapies is being filled in part by recent successes with immune checkpoint inhibitors (ICIs) targeting the programmed cell death receptor 1 and programmed death ligand 1 (PD-L1). Although single-agent ICIs had limited activity, exploration of rational combinations has yielded 2 new FDA approvals for atezolizumab and pembrolizumab in combination with chemotherapy, leading to a new standard of care for patients with PD-L1-positive disease. Two FDA-approved companion diagnostic PD-L1 assays are available to identify patients eligible for immunotherapy treatment, but other biomarkers of response are also being examined. Ongoing clinical trials are also evaluating a range of targeted therapies as combination partners, which may have immunomodulatory effects in addition to their main mechanism of action, complementing the activity of ICIs. This article will evaluate the current and emerging clinical trends in the use of ICIs as part of combination regimens in the treatment of patients with metastatic TNBC.