Neoadjuvant Immune Checkpoint Blockade for Breast Cancer: A Meta-Analysis

Abstract

Background: The application of immune checkpoint blockade (ICB)-based neoadjuvant therapy has been approved in breast cancer since 2021. However, no meta-analyses have systemly evaluated its efficacy and safety in randomized and non-randomized settings. Additionally, there exists controversy about which specific population can benefit from this strategy.

Methods: MEDLINE and EMBASE were systematically searched from inception to September 2024 was conducted for all prospective clinical trials of ICB-based neoadjuvant therapy in patients with breast cancer without language restriction. Pathological and survival outcomes and adverse events were pooled to estimate the efficacy and safety.

Findings: Here, among 22 eligible trials with 6134 women, there were 11 randomized studies with 5574 patients. Pooled pathological complete response (relative risk [RR], 1.38; 95% CI, 1.20-1.58), event-free survival (hazard ratio, 0.67; 95% CI, 0.54-0.81), and overall survival (hazard ratio, 0.56; 95% CI, 0.354-0.91) favored ICB-based neoadjuvant therapy over conventional treatment. Moreover, the benefits of event-free survival were independent of PD-L1 expression (Pinteraction=0.57) and previous pathological complete response (Pinteraction=0.37). Combining ICB with conventional neoadjuvant treatment significantly increased the risk of high-grade treatment-related adverse event (RR, 1.06; 95% CI, 1.01-1.12), treatment-related serious adverse event (RR, 1.57; 95% CI, 1.26-1.94), treatment discontinuation due to treatment-related adverse event (RR, 1.47; 95% CI, 1.14-1.90), and potentially fatal adverse event (RR, 2.25; 95% CI, 0.80-6.31). 

Interpretation: The addition of ICB to conventional neoadjuvant treatment is associated with favorable clinical outcomes and importantly, greatly increases severe toxicities. Clinicians should meticulously monitor patients for adverse events to minimize the risk of treatment discontinuation in individuals with potentially curable breast cancer. Future research needs to better define patient stratification and optimize treatment approaches that could derive benefit from ICB-based neoadjuvant therapy while minimizing the risk of severe toxicity.

Funding: This work was funded by National Natural Science Foundation of China (No. 82373367).

Declaration of Interest: We declare no competing interests.

Keywords: neoadjuvant therapy, immune checkpoint blockade, Breast cancer, Toxicity, pathologic complete response, event free survival