Combination immunotherapy strategies for triple-negative breast cancer: current progress and barriers within the pharmacological landscape

ABSTRACT

Introduction

Triple-negative breast cancer (TNBC) is a breast cancer subtype characterized by poorer prognosis. Despite that TNBC can display immunogenic features, anti-PD(L)1 monotherapy strategies have resulted in disappointing results, underscoring the need to optimize their use in TNBC. Among many, combining immunotherapy with other agents to exploit the synergistic effect of different drugs has been explored. Such a combination approach led to the approval of immune checkpoint inhibitors (ICIs) plus chemotherapy in both metastatic and early setting. Nevertheless, primary or secondary resistance to ICIs remains a major hurdle to overcome, with a major need to explore novel combination strategies.

Areas covered

This review summarizes the biological rationale, current evidence, and ongoing clinical trials of immunotherapy combined with novel immunotherapeutics, chemotherapy, targeted compounds, and antibody-drug conjugates.

Expert opinion

The treatment landscape of TNBC is in continuous changes. ICIs are now part of the clinical practice; however, several unmet needs still remain, including the need to overcome resistance and prolong benefit of ICIs. Exploiting synergism between different agent has emerged as an attractive strategy to extend the benefit obtained with ICIs. The goal of future research will be to unveil the mechanisms underlying resistance to ICIs and to identify better biomarkers for patient selection.

KEYWORDS:

• antibody-drug conjugates
• combination
• chemotherapy
• immunotherapy
• immune checkpoint inhibitors
• PARP inhibitors
• synergy
• targeted therapy
• triple-negative breast cancer
• TNBC

Article highlights

• Triple-negative breast cancer (TNBC) is the most immunogenic subtype of breast cancer, characterized by the poorest prognosis.

• Single agent immunotherapy agents have reported disappointing results in TNBC, underscoring the need to identify new strategy to optimize their use is this setting.

• A strong biological rationale supports the combination of immunotherapy with other compounds such as chemotherapy, targeted agents, or antibody-drug conjugates.

• Encouraging safety and activity signals have been reported for combinatorial regimens.

• Research efforts are needed to optimize combination treatments, understand mechanism of resistance, and identify better biomarkers for patient selection.

Declaration of interest

G Curigliano received honoraria for speaker, consultancy, or advisory rule from AstraZeneca, Roche, Pfizer, Novartis, Seattle Genetics, Lilly, Ellipses Pharma, Foundation Medicine, Daiichi Sankyo, and Samsung. 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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.