Emerging Therapeutic Drugs in Metastatic Triple-Negative Breast Cancer

Abstract

Metastatic triple-negative breast cancer (TNBC) is a heterogeneous disease with a poor prognosis and currently with few treatment options. Treatment of these patients is highly based on systemic chemotherapy. Some targeted drugs were recently approved for these patients: two poly(ADP-ribose) polymerase inhibitors in patients with germline BRCA1/2 mutations (olaparib and talazoparib), immune checkpoint inhibitors in association with chemotherapy if programmed death-ligand 1 positive (atezolizumab plus nabpaclitaxel and pembrolizumab plus chemotherapy [nabpaclitaxel, paclitaxel, and carboplatin plus gemcitabine]), and an antibody-drug conjugate sacituzumab-govitecan in heavily pretreated patients (at least 2 previous lines for the metastatic setting). Combinations using these and other targeted treatment options are under investigation in early and late clinical trials, and we will probably have some practice-changing results in the new future. Other targeted drugs explored in phase II and phase III clinical trials are PI3K/AKT pathway inhibitors and androgen receptor antagonists in patients with alterations in these signaling pathways. The definition of molecular subtypes has been essential for the development of these treatment strategies. Soon, the treatment of metastatic TNBC could be based on personalized medicine using molecular testing for targeted drugs instead of only systemic chemotherapy. The authors present a review of emerging treatment options in metastatic TNBC, focusing on targeted drugs, including the recent data published in 2020.

Keywords: PARP inhibitors; PI3K/AKT pathway; Triple-negative breast cancer; androgen receptor antagonists; immune checkpoint inhibitors; platinum chemotherapy; sacituzumab-govitecan.

Figure 1.

Proposed treatment algorithm for the treatment of mTNBC, including the approved drugs. *If PD-L1 ⩾1% and disease-free survival from (neo)adjuvant ChT >12 months. "If PD-L1(CPS) ⩾10% and disease-free survival from (neo)adjuvant ChT >6 months. If both PD-L1 and germline BRCA1/2 are positive, there are no data on which is the best approach. **Standard chemotherapy includes taxanes, anthracyclines, antimetabolites, and microtubule inhibitors. Carboplatin is an alternative with comparable efficacy and a better toxicity profile than docetaxel. A drug combination or single-agent chemotherapy could be used, depending on the disease’s extension or rapid progression. ***If previous anthracycline and a taxane in the (neo)adjuvant or metastatic setting. ChT indicates chemotherapy; CPS, combined positive score; mTNBC, metastatic triple-negative breast cancer; PD-L1, programmed death-ligand 1; TNBC, triple-negative breast cancer.