Efficacy and Safety Ranking of HER2-Targeted TKIs in Advanced Breast Cancer: A Bayesian Network Meta-Analysis

Why clinicians should know about it

• Picked for Epidemiology (top studies of the week, 20 September 2026).

Abstract

OBJECTIVE: To compare the efficacy and safety of HER2-targeted tyrosine kinase inhibitors (TKIs) in patients with HER2-positive advanced or locally advanced breast cancer using a Bayesian network meta-analysis and to provide comparative evidence for individualized treatment decisions. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for randomized controlled trials evaluating HER2-targeted TKIs in patients with HER2-positive advanced or locally advanced breast cancer. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were assessed as efficacy outcomes, while treatment-related adverse events were evaluated as safety outcomes. A Bayesian network meta-analysis was performed using R (version 4.2.2) and Stata (version 16.0). Treatments were ranked according to the surface under the cumulative ranking curve (SUCRA). The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD420250650274). RESULTS: Fourteen randomized controlled trials involving 5,289 patients were included. According to SUCRA rankings, pyrotinib plus capecitabine (Pyrotinib_C) showed the highest probability of favorable ranking PFS, ORR, and DCR. Tucatinib combined with trastuzumab and capecitabine (Tucatinib_T_C) demonstrated the highest probability of favorable OS ranking. Regarding safety, pyrotinib combined with trastuzumab and capecitabine (Pyrotinib_T_C) was associated with the highest incidence of serious adverse events, diarrhea, and hand-foot syndrome, whereas Pyrotinib_C showed the highest incidence of anemia and lapatinib plus capecitabine (Lapatinib_C) demonstrated the highest incidence of rash. CONCLUSION: Among currently available HER2-targeted TKIs, Pyrotinib_C showed the highest probability of favorable ranking for PFS and tumor response outcomes, whereas Tucatinib_T_C showed the highest probability of favorable OS ranking. However, pyrotinib-containing regimens were associated with a higher risk of treatment-related toxicities. These findings highlight the importance of balancing efficacy and safety when selecting HER2-targeted TKI therapies and support individualized treatment strategies for patients with HER2-positive advanced breast cancer.

Abstract as published, via PubMed.