Atezolizumab versus Pembrolizumab in The Treatment of Advanced Triple-Negative Breast Cancer: A Bayesian Network Meta-Analysis of ITT and PD-L1 Positive Populations

Background Immune checkpoint inhibitors (ICIs) combined with chemotherapy are a standard treatment for advanced or metastatic triple-negative breast cancer (mTNBC). However, comparative evidence regarding relative efficacy and optimal use of different ICI regimens, specifically atezolizumab (A) versus pembrolizumab (P), remains limited. This study aims to evaluate the comparative efficacy and ranking of ICIs + chemotherapy regimens in treating advanced TNBC. Methods This study conducted a Bayesian network meta-analysis of phase III randomized controlled trials (RCTs) comparing ICI + chemotherapy versus chemotherapy alone in mTNBC patients following PRISMA 2020 guidelines. Outcomes analysed included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in both intention-to-treat (ITT) and PD-L1-positive populations. Indirect comparison was performed using R software (v.4.4.0). Results The network analysis included six studies from four RCTs (n = 2,776). A + CT (Odd ratio (OR) 1.36; 95% CrI 1.13–1.64) and P + CT (OR 1.18; 95% CrI 0.88–1.56) both showed improved ORR vs. chemotherapy alone in the ITT population. This benefit was most pronounced in the PD-L1-positive population, where A + CT demonstrated the highest ORR (OR 1.64; 95% CrI 1.26–2.13). A + CT consistently ranked highest by SUCRA for short-term efficacy measures (ORR, DCR, PFS) in the PD-L1-positive population, and also achieved the highest SUCRA rank for long-term OS (36 months) in this subgroup. Conversely, P + CT achieved the highest SUCRA rank for long-term OS in the heterogeneous ITT population. Conclusion Both ICI regimens demonstrate clinical benefit. While A + CT is favoured for high probability of early response in PD-L1-positive patients, the trend for superior long-term OS with P + CT in the ITT population underscores the need to carefully weigh treatment goals, strongly supporting PD-L1 status as a key predictive factor. However, this trend favoring P + CT in the ITT population is likely attributable to the statistical dilution of A + CT efficacy caused by methodological confounders in certain atezolizumab trials.