Clinical implications of peripheral blood biomarkers in patients with advanced breast cancer treated with trastuzumab emtansine and trastuzumab deruxtecan.

BACKGROUND

Development of antibody-drug conjugates, including trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), has improved the outcomes of patients with HER2-positive breast cancer. We compared the association between peripheral blood biomarkers and outcomes in patients with breast cancer treated with T-DM1 and T-DXd.

METHODS

Eighty-five women treated with T-DM1 (n = 40) or T-DXd (n = 45) for advanced disease were evaluated. Overall survival (OS) and OS after the end of treatment (EOT) were compared based on changes in absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) between baseline and EOT.

RESULTS

In the T-DM1 group, patients with a low NLR at EOT had significantly longer OS after EOT than those with a high NLR (p = 0.007), and patients with a high ALC at EOT had longer OS after EOT (p = 0.071). In the T-DXd group, the ALC and NLR were not associated with OS. The exploratory subgroup analysis suggested that patients with high ALC at EOT had better OS after EOT (p = 0.038) in the T-DXd (HER2-low) group (n = 19), whereas ALC and NLR were not associated with the outcome in the T-DXd (HER2-positive) group (n = 26). Multivariable analysis revealed that the NLR at EOT was an independent prognostic factor for OS after EOT, after adjusting for clinicopathological factors, in the T-DM1 group (p = 0.019).

CONCLUSION

Immune status may influence treatment outcomes in the T-DM1 and T-DXd (HER2-low) groups. Conversely, in the T-DXd (HER2-positive) group, the treatment outcome was independent of immune status.