Investigational immunomodulatory drugs for enhancement of triple negative breast cancer (TNBC) immunotherapy: early phase development

ABSTRACT

Introduction

Immunotherapy through the blockade of PD1-PDL1 axis has shown to improve outcomes in advanced and early triple negative breast cancer (TNBC). To further enhance immune-stimulation, and ultimately improve patient outcomes, a wide variety of next-generation immunotherapies (NGIO) is being developed for this disease.

Areas covered

In the present article, we discuss the immune landscape of TNBC and recapitulate the rationale and available clinical evidence of NGIO under early phase development for TNBC, highlighting challenges and opportunities in this emerging field of research.

Expert opinion

Multiple immunotherapeutic strategies beyond PD-(L)1 blockade have been tested for TNBC, including the targeting of further inhibitory checkpoints, the agonism of costimulatory molecules, the intratumoral administration of immunotherapies and cancer vaccines. Most of these strategies have demonstrated to be safe in early clinical trials, with some exhibiting early signs of antitumor activity. To optimally harness the potential of NGIO, a refined patient selection based on emerging immune biomarkers will be required, through an adaptation of immunotherapeutic strategies based on patient and tumor characteristics. More mature data from ongoing clinical trials, added to the progressively increasing knowledge on breast cancer immune landscape, will hopefully clarify the role of NGIO for the treatment of TNBC.

KEYWORDS:

• Immunotherapy
• triple negative breast cancer
• TNBC
• next-generation immune-checkpoint inhibitors
• clinical trials
• breast cancer

Article Highlights

• Triple negative breast cancer (TNBC) has recently entered the immunotherapy era, with PD-(L)1 blockade showing to improve outcomes both in the advanced and early setting.

• Next-generation immunotherapies (NGIO) are being developed, in the attempt to further improve patients’ outcomes.

• Clinical evidence in this setting has recently emerged, with early phase trials of anti-LAG3, anti-TIM3, and anti-ICOS antibodies reporting an overall good safety and initial signs of antitumor activity.

• Results from a wide variety of ongoing trials are highly awaited, to identify the optimal way to harness the immune system for TNBC treatment.

• An improved integration of predictive biomarkers and clinical features will be required to enhance the value of immune-modulating strategies in TNBC.

Declaration of interest

G Curigliano received honoraria for speaker, consultancy, or advisory rule from 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

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

Additional information

Funding

This paper was not funded.