Peter E Hall1, Peter Schmid2,3. 1. Department of Medical Oncology, St Bartholomew's Hospital, King George V Building, West Smithfield, London, EC1A 7BE, UK. peter.hall12@nhs.net. 2. Department of Medical Oncology, St Bartholomew's Hospital, King George V Building, West Smithfield, London, EC1A 7BE, UK. 3. Barts Cancer Institute, Queen Mary University of London, London, UK.
Abstract
PURPOSE: The use of immune checkpoint inhibitors in combination with chemotherapy for the treatment of triple-negative breast cancer is becoming more widespread as efficacy data accumulates. However, outcomes remain less than optimal and not all patients benefit from treatment. The aim of this article is to review the emerging chemoimmunotherapy strategies for triple-negative breast cancer. METHODS: Searches were undertaken on Pubmed and Clinicaltrials.gov for relevant publications and trials. RESULTS: Preclinical and clinical data have provided insights into the differing immunomodulatory effects of chemotherapy agents, highlighting the immunostimulatory properties of anthracyclines. Mechanisms of resistance to immune checkpoint inhibition are discussed and the potential role of phosphatidylinositol 3-kinase (PI3K)/AKT and MAPK/ERK kinase (MEK) inhibitors in overcoming resistance. Finally, the emerging therapeutic class of antibody-drug conjugates for triple-negative breast cancer in combination with immune checkpoint inhibitors is reviewed. CONCLUSIONS: The type and sequence of chemotherapy agents play an important role in optimising the response to immune checkpoint inhibitors. Antibody-drug conjugates in combination with immune checkpoint inhibitors are a promising area of development.
PURPOSE: The use of immune checkpoint inhibitors in combination with chemotherapy for the treatment of triple-negative breast cancer is becoming more widespread as efficacy data accumulates. However, outcomes remain less than optimal and not all patients benefit from treatment. The aim of this article is to review the emerging chemoimmunotherapy strategies for triple-negative breast cancer. METHODS: Searches were undertaken on Pubmed and Clinicaltrials.gov for relevant publications and trials. RESULTS: Preclinical and clinical data have provided insights into the differing immunomodulatory effects of chemotherapy agents, highlighting the immunostimulatory properties of anthracyclines. Mechanisms of resistance to immune checkpoint inhibition are discussed and the potential role of phosphatidylinositol 3-kinase (PI3K)/AKT and MAPK/ERK kinase (MEK) inhibitors in overcoming resistance. Finally, the emerging therapeutic class of antibody-drug conjugates for triple-negative breast cancer in combination with immune checkpoint inhibitors is reviewed. CONCLUSIONS: The type and sequence of chemotherapy agents play an important role in optimising the response to immune checkpoint inhibitors. Antibody-drug conjugates in combination with immune checkpoint inhibitors are a promising area of development.
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