Immune-based combinations for metastatic triple negative breast cancer in clinical trials: current knowledge and therapeutic prospects

ABSTRACT

Introduction

Immune checkpoint inhibitor (ICI) monotherapy appears to be effective in a small cohort of patients with metastatic triple negative breast cancer (mTNBC). This supports the exploration of strategies for increasing the efficacy of immunotherapy. To enhance overall response and clinical outcomes, several immune-based combinations are being investigated.

Areas covered

The authors present a synopsis of current, state-of-art immune-based combinations in this setting and reflect on future possibilities. They shed light on recently presented and published clinical trials and ongoing studies. A literature search was conducted in October 2021; in addition, abstracts of international cancer meetings were reviewed.

Expert opinion

Clinical trials suggest that ICI monotherapy could be beneficial in a minority of mTNBC patients; conversely, several immune-based combinations have reported notable results in recently presented or published studies. Some of these combination strategies have been approved for mTNBC – as in the case of chemoimmunotherapy in PD-L1 positive patients. Numerous trials are investigating novel ICI-based combinations and their results are eagerly awaited.

KEYWORDS:

• Breast cancer
• triple negative breast cancer
• immunotherapy
• combinations
• immune checkpoint inhibitors
• pembrolizumab
• sacituzumab govitecan

Funding

This paper was not funded

Article Highlights

• Despite notable advances in the management of TNBC, the disease is a challenging malignancy to treat and is hence an area of intense interest.

• Immune checkpoint inhibitor (ICI) monotherapy appears to be effective in a small cohort of patients with metastatic triple negative breast cancer (mTNBC). The results of ICI monotherapy support the exploration of strategies for increasing the efficacy of immunotherapy in this patient population.

• A widely used strategy in cancer immunotherapy is based on the combination of ICIs with each other or with other anticancer agents, including systemic chemotherapy, PARP inhibitors, targeted therapies.

• Chemoimmunotherapy has become the new first-line treatment in metastatic TNBC patients with elevated CPS or PD-L1 overexpression.

• Several phase II and III clinical studies evaluating immune-based combinations with novel, investigational agents are ongoing; the results of these trials have the potential to modify the first-line treatment landscape of TNBC.

• The identification of biomarkers predictive of response to immune-based combinations is key for progress. This could orient future treatment algorithms on the basis of safety profiles and clinical benefits.

Declaration of interest

The authors have no 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.