Current and emerging biologic therapies for triple negative breast cancer

ABSTRACT

Introduction

Triple negative breast cancer, defined by a lack of estrogen receptor, progesterone receptor, or human epidermal growth factor2, accounts for approximately 15% of breast cancer patients. Treatment options have historically been limited to chemotherapy, which has significant toxicity and a suboptimal impact on the five-year relapse rate and survival.

Areas covered

Transcriptomic analyses reveal that TNBC is biologically heterogenous. Predictive biomarkers based on the distinct biology of the different subtypes of TNBC should identify patients that will derive the greatest benefit from a specifically targeted therapeutic agent. Two biomarker-driven treatments have recently been approved: poly-ADP ribose polymerase inhibitors for patients with germline BRCA mutations and atezolizumab in combination with nab-paclitaxel for patients expressing PD-L1 on tumor-infiltrating immune cells.

Expert opinion

Identifying informative predictive biomarkers is critical for the optimal development of targeted drugs for TNBC. Some targeted agents, such as the antibody-drug conjugate sacituzumab govitecan-hziy and the precision medicines capivasertib and ipatisertib, have already shown promising results in early clinical trials, and the results of definitive phase 3 trials are eagerly awaited. Additionally, testing novel immunotherapies and other targeted agents in earlier stages of disease, particularly the neoadjuvant setting, is a high priority.

KEYWORDS:

• Breast cancer
• immunotherapy
• metastatic
• neoadjuvant
• targeted therapy

Article highlights

• Treatment options for triple negative breast cancer (TNBC) have historically been limited to chemotherapy.

• The PD-L1 inhibitor atezolizumab combined with nab-paclitaxel is associated with an overall survival benefit and is a new standard of care for patients with metastatic PD-L1+ TNBC.

• In neoadjuvant therapy for early TNBC, adding pembrolizumab to standard chemotherapy increases the rate of pathologic complete response.

• The PARP inhibitors olaparib and talazoparib are approved therapies for patients with metastatic TNBC and a germline mutation in BRCA 1/2.

• The novel antibody drug conjugate sacituzumab govitecan-hziy is approved for patients with metastatic TNBC who have progressed on at least 2 prior lines of therapy for advanced disease.

• Additional immunotherapies and targeted therapies are under active clinical development for early and advanced TNBC.

Declaration of interest

L Emens reports the following potential conflicts of interest: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Celgene, Chugai, Gritstone, MedImmune, MacroGenics, Peregrine, Replimune, Roche, Syndax, Shionogi, Vaccinex (honoraria); AstraZeneca, Bayer, BMS, Genentech, MacroGenics, Novartis, Replimune, Roche, Vaccinex (travel expenses); Aduro Biotech, AstraZeneca, Bolt, Breast Cancer Research Foundation, Corvus, Department of Defense, EMD Serono, Genentech, HeritX, MaxCyte, Merck, Roche, Silverback, Tempest (research funding); Aduro Biotech (royalties). S Shaikh reports no conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One of the reviewers on this manuscript declares the following conflicts of interests: Consultant/Advisory fees: Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion. Principal/sub-Investigator of ClinicalTrials: Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveopharmaceuticals, Bayer, Beigene, Blueprint, BMS, BoeringerIngelheim, Celgene, Chugai, Clovis, DaiichiSankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 biomedicine, Incyte, InnatePharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, LytixBiopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, NektarTherapeutics, Novartis, Octimet, Oncoethix, OncopeptidesAB, Orion, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.