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

Abstract

e13010 Background: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) showing significant promise in treatment of metastatic HER2+ and HER2-low breast cancer. This systematic review and metaanalysis,pooling data from the latest randomised controlled trials aimed to evaluate the safety and efficacy of T-DXd in this patient population. Methods: A systematic literature review was conducted by searching PubMed, EMBASE, and Cochrane Library for Randomised controlled trials that assessed efficacy and safety of Trastuzumab Deruxtecan( T-DXd) published up to January 2025.The intervention was T-DXd and the control was either physicians choice of therapy or chemotherapy or Trastuzumab Emtansine( T-DM1).The primary endpoint was progression-free survival(PFS). Secondary endpoints were overall survival (OS) and incidence of adverse events. Hazard ratios with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using the I² statistic. Results: Our analysis included four studies with a total of 2555 patients. The results showed that patients receiving T-DXd had a significant improvement in progression-free survival (PFS) compared to those in the control group with a hazard ratio (HR) of 1.54 (95% CI, 1.34–1.78), indicating strong effectiveness in slowing disease progression. Overall survival was also better in the T-DXd group as compared to the control group with a HR of 1.86 (95% CI, 1.61–2.16).The adverse adverse events were similar in both groups with a Risk ratio of 1.16 (95% CI, 0.87–1.54) which was not statistically significant. In a further subgroup analysis, we excluded the study using T-DM1 as the control and the results were similar showing T-DXd significantly improved PFS, with a HR of 1.63 (95% CI, 1.40-1.90), reinforcing its strong clinical benefit in slowing disease progression. Conclusions: T-DXd has proven to be highly effective for treating metastatic HER2-+ and HER2-low breast cancer, providing an important option for patients with advanced disease. However, treatment is associated with notable side effects. This highlights the importance of carefully selecting patients and closely monitoring them to manage potential risks. Future research should focus on optimizing treatment strategies and exploring methods to enhance safety profiles. Baseline characteristics of studies. References Study design Study arms Total number of patients Median age(years) Bardia et al. RCT T-DXd vs physicians choice 866 57.5 Andre et al. RCT T-DXd vs physicians choice 608 54.2 Modi et al. RCT T-DXd vs physicians choice 557 56.8 Cortes et al. RCT T-DXd vs T-DMi 524 54.3 RCT: Randomised controlled trial. T-DXd: Trastuzumab Deruxtecan. T-DMi: Trastuzumab Emtansine.