Efficacy and Safety of Adding Immune Checkpoint Inhibitors to Neoadjuvant Chemotherapy Against Triple-Negative Breast Cancer: A Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Immune checkpoint inhibitors (ICIs) have shown promising anti-tumor activity in multiple malignances including breast cancer. However, the responses can vary. This meta-analysis was conducted to evaluate the efficacy and safety profile of adding ICIs to neoadjuvant chemotherapy against triple-negative breast cancer (TNBC) and assess correlation of PD-L1 tumor status with responses.

Methods: Eligible studies were retrieved from the PubMed, Embase, and Web of Science databases. Randomized controlled trials (RCTs) that investigated ICI-containing versus ICI-free neoadjuvant therapy were included in this study. Meta-analyses were performed using Review Manager Version 5.2 software.

Results: This study included four RCTs containing 1795 patients with early TNBC. Compared with ICI-free neoadjuvant therapy, ICI-containing neoadjuvant therapy significantly increased the pathological complete response (pCR) rates in TNBC (odds ratio [OR] = 2.14, 95% confidence interval [CI]: 1.37-3.35, P < 0.001). In subgroup analysis, the addition of ICI to neoadjuvant chemotherapy was significantly associated with increased pCR rate in both PD-L1-positive TNBC (OR = 1.79, 95% CI: 1.33-2.41, P < 0.001) and PD-L1-negative TNBC (OR = 1.84, 95% CI: 1.14-2.99, P = 0.01). Patients with TNBC receiving ICI-containing neoadjuvant therapy had a better event-free survival (hazard ratio = 0.66, 95% CI: 0.48-0.89, P = 0.007) than those who receiving ICI-free neoadjuvant therapy. A significantly higher risk of adverse events including adrenal insufficiency, increased aspartate aminotransferase, dry skin, hepatitis, hyperthyroidism, hypothyroidism, infusion related reaction, pyrexia, and stomatitis was associated with ICI-containing neoadjuvant therapy.

Conclusion: ICI-containing neoadjuvant therapy significantly increased the pCR rate in TNBC patients, independently of PD-L1 status. The addition of ICI to neoadjuvant chemotherapy may be considered an option for TNBC patients.

Keywords: immune checkpoint inhibitors (ICI); meta-analysis; neoadjuvant chemotherapy; pathological complete response; triple-negative breast cancer (TNBC).

Figure 1

Flow chart of the literature search and study selection.

Figure 2

Forest plots of meta-analyses of pathological complete response (pCR). Immune checkpoint inhibitor (ICI)-containing neoadjuvant therapy compared with ICI-free neoadjuvant therapy for triple-negative breast cancer (TNBC).

Figure 3

Forest plots of subgroup meta-analyses of pCR based on PD-L1 status. (A) ICI-containing neoadjuvant therapy compared with ICI-free neoadjuvant therapy in TNBC patients with PD-L1-positive tumors. (B) ICI-containing neoadjuvant therapy compared with ICI-free neoadjuvant therapy in TNBC patients with PD-L1-negative tumors.

Figure 4

Forest plots of meta-analyses for event-free survival (EFS). (A) ICI-containing neoadjuvant therapy compared with ICI-free neoadjuvant therapy for TNBC. (B) Anti-PD-1-containing neoadjuvant therapy compared with ICI-free neoadjuvant therapy for TNBC.