Immunotherapy for triple negative breast cancer: How can pathologic responses to experimental drugs in early-stage disease be enhanced?

ABSTRACT

Introduction

The treatment landscape of early triple-negative breast cancer (TNBC) has recently expanded after the Food and Drug Administration (FDA) approval of pembrolizumab in combination with neoadjuvant chemotherapy. The addition of this immune checkpoint inhibitor (ICI) has shown significantly increased pathological complete response (pCR) rate and event-free survival (EFS) in the KEYNOTE-522 phase III trial. Several additional studies are ongoing with the goal of further improving the outcomes and achieving an optimal integration of ICIs in the treatment of TNBC.

Areas covered

The article examines pCR and survival rates in TNBC. It appraises clinical trials investigating neoadjuvant ICIs for TNBC and the improvement of pCR rates (biomarker-driven escalation of treatment, optimization of chemotherapy backbone, and addition of locoregional treatments or innovative agents). Insights into the role of pCR as a surrogate endpoint and the possibility of enhancing pCR rates for women affected by early TNBC are offered.

Expert opinion

The pharmacopoeia of early TNBC is growing and becoming more heterogeneous with the advent of ICIs; to enhance the clinical benefit of patients, it is necessary to develop response endpoints that consider the mechanism of action of experimental drugs, to optimize patient selection through validated biomarkers, and to compare the most promising treatment strategies in randomized clinical trials.

KEYWORDS:

• Triple-negative breast cancer
• immune checkpoint inhibitors
• pathological complete response
• predictive biomarkers

Article highlights

• Neoadjuvant chemotherapy (NACT) based on anthracyclines, cyclophosphamide, and taxanes (with or without carboplatin) have represented the historical standard of care for triple-negative breast cancer.

• The addition of immune checkpoint inhibitors to NACT has recently shown a significant pCR and EFS benefit in this population.

• New strategies are being explored to further enhance pCR rates, including biomarker-driven escalation of treatment, optimization of chemotherapy backbone, and addition of locoregional treatments or innovative agents.

• The pharmacopoeia of TNBC is becoming more heterogeneous with the advent of IO agents, including ICIs. To enhance the clinical benefit, it will be necessary to develop response endpoints considering the mechanism of action of experimental drugs, to optimize patient selection through validated biomarkers, and to compare the most promising treatment strategies in randomized clinical trials.

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Declaration of interest

PT served as advisor/consultant for AstraZeneca. GC 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has intellectual property in a dendritic cell vaccine. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.