Efficacy and safety of antibody-drug conjugates in pretreated HER2-low metastatic breast cancer: A systematic review and network meta-analysis.
INTRODUCTION: Antibody-drug conjugates (ADCs) trastuzumab-deruxtecan (T-DXd) and sacituzumab-govitecan (SG) provided significant progression-free survival (PFS) and overall survival (OS) improvements over chemotherapy (CT) in pretreated hormone receptor-positive (HR+) and triple-negative (TN)/HER2-l...
| Autores: | , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | INCLIVA |
| Repositorio: | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| OAI Identifier: | oai:incliva.fundanetsuite.com:p19490 |
| Acceso en línea: | https://incliva.portalinvestigacion.com/publicaciones/19490 |
| Access Level: | acceso abierto |
| Palabra clave: | HER2-low Metastatic breast cancer Network meta-analysis Sacituzumab govitecan Trastuzumab deruxtecan |
| Sumario: | INTRODUCTION: Antibody-drug conjugates (ADCs) trastuzumab-deruxtecan (T-DXd) and sacituzumab-govitecan (SG) provided significant progression-free survival (PFS) and overall survival (OS) improvements over chemotherapy (CT) in pretreated hormone receptor-positive (HR+) and triple-negative (TN)/HER2-low metastatic breast cancer (MBC). However, no direct comparison between the two exists, nor with the more recent datopotamab-deruxtecan (Dato-DXd). METHODS: We conducted a network meta-analysis (NMA) to compare efficacy and safety of T-DXd and SG in CT-pretreated HR+ and TN/HER2-low MBC and assess their benefit over standard CT, exploring also a comparison with Dato-DXd. Hazard ratios (HRs) with 95 % confidence intervals (CI) were calculated for PFS/OS. P-score was used for treatment ranking. RESULTS: Three RCTs (956 patients) were included in the primary analysis and 5 (1,445) in the exploratory NMA with Dato-DXd. In HR+/HER2-low, T-DXd showed no significant difference in PFS and OS when compared to SG. Similarly, in TN/HER2-low, PFS and OS did not differ significantly between the two ADCs. The P-score analysis favored T-DXd over SG in HR+/HER2-low in PFS (0.90 vs. 0.60) and OS (0.89 vs. 0.60). SG was favored over T-DXd in OS in TN/HER2-low (0.80 vs. 0.69). Similar results were obtained for HR+ MBC when including Dato-Dxd, which showed the worst performance, while T-DXd was the only ADC significantly outperforming CT in OS. The ADCs showed significantly better PFS and OS than CT in HR+/HER2-low and TN/HER2-low (all p < 0.001). SG had higher rates of neutropenia, diarrhea and alopecia vs. T-DXd, which showed more thrombocytopenia, fatigue and nausea. Pneumonitis and cardiotoxicity were typically T-DXd-related, and T-DXd showed more toxicity-related discontinuations. CONCLUSIONS: Similar efficacy with T-DXd and SG in HER2-low MBC was observed, regardless of HR status. Safety profile, local drug-approval criteria and guidelines, patients' preferences and overall quality of evidence should ultimately guide therapeutic decision-making. Dato-DXd role remains uncertain. |
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