Efficacy and safety of antibody-drug conjugates in pretreated HER2-positive advanced breast cancer: a network meta-analysis of randomized controlled trials
In brief
T-DXd lowers progression-or-death hazard 82% versus chemotherapy plus a kinase inhibitor
In a network analysis of seven trials and 3,160 patients with pretreated HER2-positive advanced breast cancer, T-DXd ranked highest for progression-free survival, with an 82% lower progression-or-death hazard than chemotherapy plus a kinase inhibitor. SHR-A1811 showed the strongest overall-survival signal, while T-DXd caused more all-grade side effects; because treatments were not compared head to head, their relative benefits remain uncertain.
- Journal
- Frontiers in pharmacology (Q1)
- Published
- 28 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Fen Liu, Yong Pan, Jinlan Li, Xiaojie Hu, Guisen Yin
- PMID
- 42865882
- DOI
- 10.3389/fphar.2026.1921830
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 17 October 2026): Network meta-analysis of HER2‑positive ADCs
Abstract
BACKGROUND: Antibody-drug conjugates (ADCs) have become the standard treatment for HER2-positive(HER2+)advanced breast cancer following the failure of trastuzumab or taxane. Nevertheless, there are no direct head-to-head trials comparing different ADCs. METHODS: We searched PubMed, Embase, the Cochrane Library and abstracts from major oncology conferences, and included phase III randomized controlled trials (RCTs) investigating HER2-targeting ADCs. We conducted a frequentist random-effects NMA, and utilized the P-score to rank the efficacy of included treatments. The outcome indicators include progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). RESULTS: Seven RCTs involving 3,160 patients and seven ADCs (T-DM1, ARX788, A166, SHR-A1811, RC48, DP303c and T-DXd) were included in our research. All ADCs showed a significant PFS benefit versus chemotherapy plus tyrosine kinase inhibitor (Chem + TKI). T-DXd showed the most favorable PFS (HR = 0.18, 95%CI: 0.13-0.25), followed by SHR-A1811 (HR = 0.22, 95%CI: 0.15-0.33) compared with Chem + TKI. SHR-A1811 showed a promising OS signal(HR = 0.31, 95% CI: 0.14-0.69), followed by T-DXd (HR = 0.41, 95% CI: 0.26-0.66) compared with Chem + TKI. For safety, T-DXd exhibited the highest odds for all-grade TRAEs relative to all included control treatments, with statistically significant differences identified when compared with T-DM1 and Chem + TKI., T-DM1 demonstrated better safety characteristics for grade ≥3 TRAEs, with a significantly lower odds of occurrence than SHR-A1811, ARX788, DP303c, and Chem + TKI. CONCLUSION: Included anti-HER2 ADCs significantly improve PFS over Chem + TKI, among which T-DXd and SHR-A1811 deliver notable survival benefits. Although T-DXd is associated with a higher odd of all-grade TRAEs and T-DM1 exhibits favourable grade ≥3 safety. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251234345, identifier CRD420251234345.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.