Abstract
PurposeSome studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients.MethodsAfter searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of programmed death protein-1/programmed cell death-Ligand 1(PD-1/PD-L1) inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations.ResultsSix RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32–2.78, P < 0.001). The pCR rate also increased in both PD-L1 positive (OR: 1.65; 95% CI: 1.26–2.16, P < 0.001) and PD-L1 negative patients (OR: 1.56; 95% CI: 1.04–2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69–3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42–2.53, P < 0.001). Three RCTs (N = 1615) reported EFS and the results showed that adding PD-1/PD-L1 inhibitors increased EFS (HR 0.65, 95% CI 0.50–0.83, P = 0.0007) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3–4 diarrhea (OR: 2.54; 95% CI: 1.21–5.32; P = 0.01), any grade of adverse effects(AEs)including vomiting (OR: 1.37; 95% CI: 1.00–1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39–15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02–8.39; P < 0.001).ConclusionsPD-1/PD-L1 inhibitors combined with chemotherapy can improve pCR rates and EFS, and with an increased incidence of some immune-related AEs compared with chemotherapy alone. NACT plus ICIs might be an option in patients with in PD-L1 positive and high-risk populations with positive nodal disease early TNBC.
Highlights
Triple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis due to its invasiveness and high recurrence and metastasis rates [1]
The results showed that patients with TNBC who received neoadjuvant chemotherapy (NACT) plus immunotherapy had a significant improvement in pathological complete response (pCR) compared with NACT alone in intention-to-treat populations (ITT) populations (OR:1.91; 95% confidence intervals (CI): 1.32–2.78, P < 0.001)
The results showed that NACT plus Immune checkpoint inhibitors (ICIs) were associated with the incidence of toxicities, regardless of the grade of adverse events (AEs) (OR: 1.19; 95% CI: 1.05–1.34; P = 0.005), or grade (See figure on page.) Fig. 3 Pooled odds ratios for pathological complete response of neoadjuvant chemotherapy plus immune checkpoint inhibitors versus neoadjuvant chemotherapy in three subgroups analysis
Summary
Triple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis due to its invasiveness and high recurrence and metastasis rates [1]. Neoadjuvant treatment is important in patients with early TNBC because it could downsize the stage, increase the chance of surgery or breast-conserving surgery, test the sensitivity of patients to chemotherapy, and assess prognosis according to the pathological response [2, 3]. Many drugs are available for the treatment of patients with TNBC, such as immunotherapy, poly ADP-ribose polymerase (PARP) inhibitors [5, 6], and other targeted therapies [4, 7, 8]. Bevacizumab can be used for the treatment of metastatic triple negative breast cancer in certain circumstances. PARP inhibitors are mainly used for breast cancer patients with germline BRCA mutation [9, 10]. Platinum and PARP inhibitors could improve pathological complete response (pCR), but platinum drugs could increase serious toxicity [11, 12]
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