Tumor microenvironment delineates differential responders to trastuzumab emtansine in HER2-positive metastatic breast cancer patients previously treated with pyrotinib: an exploratory biomarker analysis of a phase II study (NJMU-BC02).

This multicenter phase II trial evaluated trastuzumab emtansine (T-DM1) in 36 patients with HER2-positive metastatic breast cancer who had progressed after pyrotinib and/or trastuzumab plus pertuzumab.

The study demonstrated:

• Objective response rate of 47.2%
• Disease control rate of 66.7%
• Clinical benefit rate of 50%
• Median progression-free survival of 6.6 months

Toxicity was manageable.

Single-cell RNA sequencing identified low cancer cell cycle activity and activation of macrophages and CD8+ T cells as potential biomarkers associated with better T-DM1 efficacy.

These findings support the use of T-DM1 after resistance to prior HER2 therapies and provide preliminary insights into predictive biomarkers for treatment response.