Effects of the Combination of Neoadjuvant Immunotherapy with Chemotherapy versus Placebo with Chemotherapy on Pathologic Complete Response in Early Triple-Negative Breast Cancer: A Systematic Review

Abstract

Introduction: One of the most aggressive forms of breast cancer is triple-negative breast cancer (TNBC). TNBC has a poor prognosis and limited therapeutic options. Therefore, therapeutic intervention is strongly suggested when treatment with the intention of cure is still possible. Chemotherapy and immune checkpoint inhibitors have already been utilized to raise the pathologic complete response (pCR) rates in early-stage TNBC patients. Objectives: The study aims to assess the efficacy of neoadjuvant immunotherapy in combination with chemotherapy, in the early-stage TNBC, with the primary endpoint of pCR (ypT0/is ypN0). Methods: The medical term “Immunotherapy”, “Pembrolizumab”, “Atezolizumab”, “Durvalumab”, “Neoadjuvant treatment”, and “Triple-negative breast cancer”, were used in Pubmed and Google Scholar to discover studies of the efficacy of immunotherapy combined with chemotherapy in early-stage TNBC by following the PICO framework up to January 2023. All phase 1, 2, and 3 clinical studies demonstrating safety and efficacy data were included. Two independent reviewers excluded the non-RCTs and other clinical studies irrelevant to the study question. Five remaining studies were reviewed and screened for the inclusion criteria, based on the relevance to the study subject and clinical outcomes. Results: Based on five studies included in this review, a combination of immunotherapy (pembrolizumab, atezolizumab, or durvalumab) with chemotherapy has shown superior effects of increasing pCR rates, compared to the chemotherapy alone, regardless of PD-L1 status, in early-stage TNBC. Adverse events were not more frequently reported with the immunotherapy compared to placebo. Conclusions: A combination of neoadjuvant immunotherapy with chemotherapy has revealed superior effects of increasing pCR rates, compared to the chemotherapy alone in early-stage TNBC, irrespective of PD-L1 status, with an acceptable safety profile. However, further studies are needed to explore this issue.