Sheraz Azhar, Medical Oncology SpR at the University Hospitals of Leicester NHS Trust and Founder of OncsCare, shared a post on LinkedIn:
“The HER2-targeted ADC landscape continues to evolve.
A phase III trial published in The Lancet Oncology 2 days ago evaluated trastuzumab rezetecan versus pyrotinib plus capecitabine in patients with previously treated HER2-positive metastatic breast cancer. The study was conducted across 50 hospitals in China and showed a significant improvement in progression-free survival with trastuzumab rezetecan.
An important nuance: pyrotinib plus capecitabine is a standard comparator in China after trastuzumab and chemotherapy, but it is not a regimen we commonly use in the UK.
In UK practice, the key question is not simply whether trastuzumab rezetecan is active, but how it compares with current HER2-directed options such as trastuzumab deruxtecan, tucatinib-based treatment, T-DM1 in selected settings, and other later-line approaches.
So for me, the interesting part of this study is less about immediate practice implications and more about the bigger sequencing question: As more HER2-directed ADCs become available, how do we decide which drug should come first, second, or later?
Key questions remain:
- Can one HER2 ADC work after progression on another?
- Do differences in payload, linker and drug-antibody ratio meaningfully overcome resistance?
- Which biomarkers should guide selection?
- How do we balance efficacy with cumulative toxicity across multiple lines?
The next decade may not be defined by discovering new HER2-targeted drugs alone, but by generating the evidence needed to use them more intelligently. Looking forward to seeing how trastuzumab rezetecan fits into the evolving HER2 treatment paradigm as further global data emerge.”
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