Treatments for human epidermal growth factor receptor 2 (HER2)–altered cancers evaluated using a tumor‑agnostic approach: A narrative review

Human epidermal growth factor receptor 2 (HER2) is a critical driver of tumorigenesis across a wide range of cancers, positioning it as a key target for tumor-agnostic therapies. Advances in HER2 therapies have shifted the treatment paradigm from histology-driven toward biomarker-driven, pan-tumor approaches. This review discusses the outcomes of approved and emerging HER2 therapies, highlighting the variability in efficacy across tumor types due to a combination of factors, such as HER2 heterogeneity, co-alterations, and tumor-specific resistance mechanisms. Although tumor-agnostic basket trials offer opportunities to evaluate HER2 therapies efficiently across multiple cancer types, challenges such as small patient populations, non-randomized designs, and heterogeneous tumor types can limit the reliability of their findings. Here, we review the available data on HER2 therapies in tumor-agnostic studies, with the goal of informing future clinical research and promoting greater appreciation of the nuances of HER2-altered cancers.