Efficacy and safety of trastuzumab deruxtecan for metastatic HER2+ and HER2-low breast cancer: A systematic review and meta-analysis

BACKGROUND: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate uesd for the treatment of HER2- positive (HER2+)breast cancer. This systematic review aimed to evaluate the efficacy and safety of T-DXd in advanced HER2-positive breast cancer. METHODS: PubMed, Web of Science and Embase databases were searched for literature on trastuzumab deruxtecan treatment for HER2-positive or low-expression breast cancer before December 30, 2024. The outcome measures were progression-free survival (PFS), overall survival (OS), objective response rates, and adverse events of any grade and grade ≥ 3. Meta-analysis of the relevant data was performed using Stata 14.0. RESULTS: A total of 2995 patients from 7 studies were included. The median PFS and median overall survival of patients in the T-DXd group were significantly longer than those of patients in the control group (mPFS HR = 0.43;95% CI:0.31-0.62, p<0.05; mOS HR = 0.72; 95% CI:0.64-0.82, p<0.05). Further subgroup analyses based on differences in hormone receptor expression, occurrence of brain metastases, visceral basal conditions, and previous lines of treatment showed that all patients in the T-DXd group had significantly longer mPFS than those in the control group (P < .05). The objective remission rate of patients in the T-DXd group was significantly higher than that of patients in the control group (RR = 2.31; 95%CI: 1.88-2.85, P<0.05). In addition, the T-DXd also increased the incidence of adverse events such as anemia, nausea, vomiting, constipation and interstitial lung disease, but the incidence of neutropenia, diarrhea, and alopecia was not significantly different between the 2 groups. No significant publication bias was observed in this study. The results of the sensitivity analysis showed high heterogeneity in mPFS, but the results obtained after excluding the DESTINY-Breast04 studies were all more robust. CONCLUSION: T-DXd has significant long-term and near-term efficacy in prolonging median overall survival, median PFS, and increasing the objective remission rate in patients with HER2-positive or low-expression breast cancer; however, the treatment is associated with notable adverse events, and physicians should be alert to the occurrence of serious adverse events when using this drug.