Dr Lenz on the Association Between HER2 Expression and Treatment Outcomes in mCRC

Heinz-Josef Lenz, MD, FACP, associate director, Clinical Research, chair, Gastrointestinal Oncology Program, codirector, Colorectal Center, University of Southern California Norris Comprehensive Cancer Center; professor, Department of Medicine, Department of Preventive Medicine, Division of Oncology, Keck School of Medicine, discusses the investigation of the association between HER2 expression and outcomes with bevacizumab (Avastin)– vs cetuximab (Erbitux)–based regimens in patients with metastatic colorectal cancer (mCRC).

In investigating the association between HER2 expression and outcomes with bevacizumab- vs cetuximab-based regimens in mCRC, Lenz says investigators addressed critical gaps in knowledge regarding the role of HER2 in this context. Drawing insights from advancements in breast and gastric cancer therapies targeting HER2, such as tucatinib (Tukysa) and fam-trastuzumab deruxtecan-nxki (Enhertu), the significance of HER2 expression in mCRC became increasingly apparent, he explains. Unlike other cancer types, there had been limited research on HER2 gene expression in mCRC, with existing studies mainly relying on immunohistochemistry (IHC), which can be challenging to use for accurate classification of HER2 expression levels, he adds.

Investigators used RNA testing in the phase 3 CALGB/SWOG-80405 trial (NCT00265850) to explore whether HER2 expression holds predictive and prognostic value in mCRC, particularly in the context of resistance to cetuximab, Lenz elucidates. This investigation shed light on whether high HER2 expression could serve as a mechanism of resistance to cetuximab, a commonly used treatment in mCRC, he continues. Investigators sought to confirm and extend previous data indicating a link between HER2 expression levels and treatment response, Lenz adds.

This comprehensive research approach elucidated the predictive potential of HER2 in guiding treatment decisions and deepened investigators’ understanding of how HER2 influences the efficacy of different therapeutic regimens, including bevacizumab- and cetuximab-based treatments, he explains. This investigation represents a critical step toward enhancing personalized treatment strategies for patients with mCRC based on HER2 status, potentially paving the way for more targeted and effective therapeutic interventions in the future, Lenz concludes.