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 (CT) are a standard treatment for advanced or metastatic triple-negative breast cancer (mTNBC). This study aims to evaluate the comparative efficacy and ranking of ICIs + CT regimens in treating advanced TNBC. METHODS: A Bayesian network meta-analysis of phase III randomized controlled trials (RCTs) comparing ICI + CT versus CT alone was conducted in advanced TNBC patients. Outcomes included objective response rate (ORR), disease control rate (DCR), landmark mortality probability ratios, and landmark progression probability ratios across intention-to-treat (ITT) and PD-L1-positive populations. Indirect comparison was performed using R software following PRISMA 2020 guidelines. RESULTS: The network analysis included four RCTs (six publications; n = 2,776). Atezolizumab (A) + CT achieved higher ORR than chemotherapy alone, especially in the PD-L1-positive population, whereas DCRs were comparable across groups. At 36 months, landmark mortality probability ratios in the ITT population were 0.68 (95% CrI 0.60-0.76) vs. 0.67 (95% CrI 0.58-0.78) for A + CT and pembrolizumab (P) + CT, respectively. In the PD-L1-positive subgroup, these ratios were 0.73 (95% CrI 0.61-0.88) vs. 0.83 (95% CrI 0.53-1.18) for A + CT and P + CT, respectively. The 36-month landmark progression probability ratios favored P + CT in the ITT cohort (0.47 vs. 0.62 for A + CT) and were comparable in the PD-L1-positive population (0.51 vs. 0.47 for A + CT). SUCRA ranking showed A + CT as having the highest probability of effectiveness for short-term outcomes in the PD-L1-positive patients. Conversely, P + CT demonstrated superior long-term survival stability in the ITT population, reinforced by restricted mean survival time (RMST) analysis. The certainty of evidence via GRADE was low to moderate. CONCLUSION: Both ICI regimens provide clinical benefit, as reflected by lower landmark mortality and progression probability ratios compared with chemotherapy. A + CT demonstrates superior initial response probabilities in PD-L1-positive patients, whereas P + CT exhibits more durable long-term outcomes in the ITT population. Regimen selection should be guided by specific clinical priorities, biomarker status, and the desired temporal profile of the therapeutic effect.