DESTINY-Breast04: Exploratory biomarker analysis

Previously, results of the phase III DESTINY-Breast04 trial demonstrated a significant benefit in progression-free (PFS) and overall survival (OS) with trastuzumab deruxtecan (T-DXd) over treatment of physician’s choice (TPC) in patients with HER2-low (IHC 1+ or 2+/ISH-negative) metastatic breast cancer. During ESMO 2022, Prof Dr Naoto Ueno (University of Hawaii Cancer Center, Honolulu, HI, USA) presented the results of an exploratory biomarker analysis of this trial. 

These biomarker analyses revealed that the clinical benefit with T-DXd was obtained regardless of the HER2 immunohistochemistry status, the baseline HER2 gene expression, the DNA damage response or cell proliferation gene expression signature, the BRCA and homologous recombination repair (HRR) status and the composition of the tumour microenvironment. Interestingly, the analysis did suggest a trend for a more pronounced treatment effect to T-DXd in patients with a higher HER2 expression at baseline and in patients with a higher level of total lymphocytes in the stroma. However, these differences were not significant and require confirmation in a more dedicated study.

As such, these results demonstrate that the clinical outcome with T-DXd is not significantly influenced by the biomarkers assessed in this analysis