Comparative efficacy of subsequent-line therapies for advanced triple-negative breast cancer: a bayesian network meta-analysis

Why clinicians should know about it

• Picked for Oncology and Radiation Oncology (top studies of the week, 26 July 2026): Bayesian NMA shows ADCs superior in later‑line advanced triple‑negative breast

Abstract

BACKGROUND: Direct head-to-head randomized comparisons among emerging therapies are limited, making it difficult to determine the optimal subsequent-line treatment for advanced triple-negative breast cancer (TNBC). This study aimed to systematically compare the relative efficacy of second- and later-line regimens using a Bayesian network meta-analysis (NMA). METHODS: PubMed, Embase, Web of Science, Cochrane Library and ClinicalTrials.gov were searched to 30 September 2025 for randomized controlled trials (RCTs) of second-/later-line advanced TNBC. A Bayesian NMA estimated effects on objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). SUCRA was used for ranking, and model convergence was assessed by Gelman-Rubin diagnostics. Single-arm studies were included only in sensitivity analyses using a down-weighted binomial model for ORR. Additional sensitivity analyses included ChemoC node splitting and evidence certainty assessment (CINeMA). RESULTS: Thirty-one RCTs and 34 single-arm studies (11,048 patients; 22 regimens) were included. Antibody-drug conjugate (ADC)-based therapies showed the most favorable efficacy overall. Sacituzumab govitecan (SG), sacituzumab tirumotecan (ST), and trastuzumab deruxtecan (T-DXd) ranked highest for ORR and PFS, with consistent benefits for SG and ST versus chemotherapy. T-DXd showed benefit mainly in HER2-low, HR-negative patients. For OS, SG and ST demonstrated clear advantages, while T-DXd showed non-significant effects. Combination chemotherapy outperformed single-agent chemotherapy for ORR and PFS. PARP inhibitors and PD-1-based regimens showed inconsistent efficacy across outcomes. Sensitivity analyses confirmed that incorporating single-arm data and separating chemotherapy nodes did not materially change treatment rankings or overall conclusions. CONCLUSION: ADCs, particularly SG and ST, were generally associated with favorable efficacy across outcomes in the subsequent-line treatment of advanced TNBC. These results may support clinical decision-making, although heterogeneity in study populations and the absence of direct comparisons highlight the need for further head-to-head trials.

Abstract as published, via PubMed.