Comparisons of survival outcomes of antibody-drug-conjugates in metastatic breast cancer: A network meta-analysis.

• DOI: 10.1200/jco.2025.43.16_suppl.e15003
• Publication Date: 2025-05-28T15:26:18Z
• Authors: Yiqun Han; Yuan Yao; Yucai Wang; Yoshito Nishimura; Yi Lin; Meng Xu Welliver; Kathryn Jean Ruddy; Robert Mutter
• Keywords: Antibody-drug conjugate

e15003 Background: Antibody-drug conjugates (ADCs) have shown substantial promise as therapies for metastatic breast cancer (mBC). However, direct comparisons of different ADC-based regimens are limited. We assessed survival outcomes in mBC patients treated with ADCs. Methods: Randomized controlled trials (RCTs) published before October 2024 were searched Medline, Embase, ClinicalTrials.gov, and Cochrane Library. Progression-free (PFS) overall surcvival (OS) extracted from the most updated publications. Participants stratified based on molecular subtypes, hormone receptor (HR) status, duration cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) treatment, sensitivity to endocrine therapy (ET). Bayesian frameworks deployed, presenting synthesized indirect using surface under cumulative ranking curve (SUCRA), hazard ratio (HR), 95% credible interval (Crl). This study was prospectively registered International Platform Registered Systemic Reviews Meta-analysis Protocols (INPLASY) (INPLASY2024110021). Results: A total 6449 12 RCTs ADCs ado-trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd), datopotamab (Dato-DXd) included analysis. Compared chemotherapy, T-DXd significantly improved PFS (HR 0.35, Crl 0.15-0.84) OS 0.56, 0.32-1.0). SG also extended 0.65, 0.43-0.97) but not PFS. In HER2+ mBC, pooled analyses revealed effective treatment terms PFS, a SUCRA 94.2%, followed by T-DM1 (58.9%), chemotherapy HER2-directed (34.2%). Synthesized mirrored outcomes. HR+/HER2- (some which HER2-low), Dato-DXd (76.1%) showed slightly superior efficacy over (67.4%) while (85.1%) advantageous (49.1%) OS. Among HR+/HER2+ (80.0%), (55.5%), (53.1%) prolonging Regarding OS, (70.3%) (60.3%) effective, comparable observed between (52.1%) (52.0%). HR-/HER2+ (78.1%), (56.1%), (51.5%) prolonged (69.4%) had benefit (62.8%) (57.6%). an advantage received CDK4/6i > months. Conclusions: network meta-analysis prominent benefits ADC-containing mBC. Our results provide valuable insights into personalized strategies patients.