What is the role of immunotherapy in breast cancer?

From the Guidelines

Immunotherapy is a crucial treatment option for certain types of breast cancer, particularly triple-negative breast cancer, and should be considered as a first-line treatment in combination with chemotherapy for patients with a PD-L1 combined positive score (CPS) of ≥ 10, as it has been shown to improve progression-free survival (PFS) and overall survival (OS) in this patient population. The role of immunotherapy in breast cancer is supported by recent studies, including the KEYNOTE-355 trial, which demonstrated that pembrolizumab plus standard chemotherapy significantly improved PFS compared with placebo plus standard chemotherapy in patients with untreated metastatic triple-negative breast cancer and a PD-L1 CPS of ≥ 10 1. Key points to consider when using immunotherapy in breast cancer include:

• The use of immune checkpoint inhibitors like pembrolizumab (Keytruda) and atezolizumab (Tecentriq) in combination with chemotherapy
• The importance of PD-L1 testing to identify patients who are most likely to benefit from immunotherapy
• The potential for immune-related adverse events, which can be managed with regular monitoring and prompt treatment
• The improved survival rates seen in patients with aggressive subtypes of breast cancer, such as triple-negative breast cancer, who receive immunotherapy as part of their treatment regimen 1. In terms of specific treatment regimens, pembrolizumab is typically administered intravenously every 3 weeks in combination with chemotherapy, such as nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin 1. Overall, immunotherapy has emerged as a valuable treatment option for certain types of breast cancer, and its use should be considered in the context of a patient's individual disease characteristics and treatment goals.

From the FDA Drug Label

for the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. in combination with chemotherapy, for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA approved test.

The role of immunotherapy in breast cancer is in the treatment of Triple-Negative Breast Cancer (TNBC), specifically:

• In combination with chemotherapy as neoadjuvant treatment for high-risk early-stage TNBC, and then continued as a single agent as adjuvant treatment after surgery.
• In combination with chemotherapy for locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10). 2

From the Research

Role of Immunotherapy in Breast Cancer

• Immunotherapy has revolutionized the treatment of solid tumor malignancies, including breast cancer, particularly triple-negative breast cancer (TNBC) 3, 4, 5, 6, 7
• The most robust data for immune checkpoint inhibitors (ICIs) exists for TNBC, with preclinical studies suggesting increased antitumoral immune response in patients with TNBC undergoing ICI treatment 3
• Clinical trials have investigated the use of ICI monotherapy in patients with metastatic TNBC, with promising results, particularly in the first-line setting and for those patients whose tumors had high programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) expression 3, 4

Biomarkers for Immunotherapy Response

• Several biomarkers have been identified as predictive of response to ICI therapy, including PD-1/PD-L1 expression, tumor mutational burden, tumor-infiltrating lymphocytes, and multigene assays capturing favorable immune cell signatures 3, 5, 6
• Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) play a crucial role in the TNBC microenvironment, and TILs can be considered as biomarkers to predict chemotherapy response in TNBC 7

Combination Therapies and Ongoing Research

• Combination of ICIs with chemotherapy has shown improved progression-free survival and overall survival benefits for patients with PD-L1 combined positive score > 10 metastatic TNBC 3
• Ongoing studies are evaluating ICI therapy in combination with chemotherapy and targeted agents for hormone receptor-positive and human epidermal growth factor receptor-positive breast cancer 3, 5
• Novel immunotherapeutic agents, including novel ICIs, cancer vaccines, adoptive cellular therapy, and oncolytic viruses, are under investigation for breast cancer treatment 3, 6