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.