Trastuzumab deruxtecan (T-DXd) monotherapy in advanced HER2-positive or HER2-low/ultralow breast cancer: An updated pooled analysis of prospective clinical trials.

Abstract

e13103 Background: The efficacy and safety of T-DXd have been established in patients with advanced HER2-positive or HER2-low/ultralow breast cancer. We aimed to provide up-to-date and comprehensive estimates of T-DXd's long-term efficacy and safety in this population. Methods: The PUBMED, ClinicalTrials.gov, and relevant international conference proceedings databases were searched on December 2024, to identify all potential eligible trials. Studies were considered eligible if they were prospective clinical trials evaluating T-DXd monotherapy in patients with advanced HER2-positive or HER2-low/ultralow breast cancer. Kaplan-Meier curves were used to reconstruct individual patient data and to conduct pooled analyses. The primary outcome analyzed was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response rate (ORR), and safety. Results: A total of 13 trials (including 4 randomized controlled trials) involving 3779 patients were included in the final analysis. Across 12 trials evaluating T-DXd monotherapy for previously treated advanced breast cancer, the ORR was 57% (95%CI: 50%-64%) with T-DXd. Both PFS and OS in HER2-positive patients were significantly longer than in HER2-low/ultralow patients. Across 4 randomized controlled trials, T-DXd led to longer PFS and OS than control treatments. For patients with brain metastases, the overall ORR was 56% (95%CI: 47%-66%), with an ORR of 52% for patients with stable/treated brain metastases, and an ORR of 48% for patients with active/untreated brain metastases. Among those with a T-DXd dose of 5.4 mg/kg, the overall incidence of grade ≥ 3 adverse events was 51% (95%CI: 47%-55%), the incidence of interstitial lung disease was 11% (95%CI: 9%-14%), and the incidence of left ventricular ejection fraction decrease was 5% (95%CI: 3%-8%). Additional efficacy and safety outcomes will be presented. Conclusions: This pooled analysis provides robust insights into the positive impact of T-DXd in advanced HER2-positive or HER2-low/ultralow breast cancer. T-DXd monotherapy results in favorable PFS, OS, and ORR for advanced breast cancer, with a generally manageable safety profile. The long-term efficacy of T-DXd is better in HER2-positive patients than in HER2-low/ultralow patients. T-DXd is effective in advanced breast cancer with brain metastases.