Activity of novel anti-HER2 agents for breast cancer based on hormone receptors expression

Excerpt

The field of pretreated HER2-positive metastatic breast cancer (MBC) has represented a major unmet need of breast oncology for decades, due to the lack of highly effective treatments. This scenario has recently been revolutionized by the emergence and FDA approval of a multiplicity of novel anti-HER2 agents, including the antibody-drug conjugate trastuzumab deruxtecan [1], the tyrosine-kinase inhibitors tucatinib [2] and neratinib [3], and the FC-engineered monoclonal antibody margetuximab [4]. Trastuzumab deruxtecan has been approved based on the impressive activity shown in a single-arm phase 2 trial [1], whereas the other three compounds have been approved based on the demonstration of a statistical advantage in progression-free survival (PFS) over the standard of care, although with variable clinical magnitude [2‐4]. In this context, no trial directly comparing these novel drugs has yet been conducted, and no biomarker is yet available to prioritize one treatment over the other. In fact, treatment choices among pretreated HER2-positive MBC patients commonly rely on cross-trials comparisons, in terms of activity, toxicity, and population enrolled [5]. Importantly, few differences in treatment are currently recommended between HER2-positive MBC patients with or without expression of hormone receptors (HR), although these are known to be very different biological entities [6]. …