Safety and Efficacy of Trastuzumab Deruxtecan for Metastatic HER2+ and HER2-low Breast Cancer: An Updated Systematic Review and Meta-Analysis of Clinical Trials.

ABSTRACT

OBJECTIVES: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) promising in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review and meta-analysis, integrating data from the latest clinical trials, aimed to evaluate the safety and efficacy of T-DXd in this patient population. METHODS: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Scopus, and Web of Science up to January 2024, focusing on clinical trials that assessed T-DXd's efficacy and safety. Eligibility criteria were based on the PICOS framework, and selected studies underwent rigorous quality assessment and data extraction. The primary outcomes were progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. A random-effects meta-analysis was performed to synthesize the data. RESULTS: Seven studies involving 2,201 patients met the inclusion criteria. The pooled analysis revealed that T-DXd significantly improved PFS (OR=0.37, 95% CI 0.27-0.52), indicating a robust efficacy in slowing disease progression. However, treatment was associated with an increased risk of anemia (OR=2.10, 95% CI 1.36-3.25), fatigue (OR=1.56, 95% CI 1.21-2.02), nausea (OR=6.42, 95% CI 4.37-9.42), vomiting (OR=6.21, 95% CI 3.14-12.25), constipation (OR=2.26, 95% CI 1.53-3.34), and notably, drug-related interstitial lung disease (OR=10.89, 95% CI 3.81-31.12). The efficacy outcomes demonstrated significant heterogeneity, which was addressed through sensitivity analysis. CONCLUSIONS: T-DXd shows significant efficacy in treating metastatic HER2+ and HER2-low breast cancer, offering a valuable therapeutic option for patients with advanced disease. However, the treatment is associated with notable adverse events, including a heightened risk of ILD. These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks. Future research should focus on optimizing treatment protocols and exploring methods to enhance safety profiles.