Dr Parikh on Available Treatment Options for HER2+ CRC

Aparna Parikh, MD, associate professor, medicine, Harvard Medical School; assistant in medicine, Hematology, Oncology, Massachusetts General Hospital; attending oncologist, Tucker Gosnell Center for Gastrointestinal Cancers, Henri and Belinda Termeer Center for Targeted Therapies, discusses currently available treatment options for patients with HER2-positive colorectal cancer (CRC), highlighting research that set the standard in this paradigm.

For patients with HER2-positive disease, there are a few treatment options to consider, Parikh begins. The first option involves the phase 2 MOUNTAINEER trial (NCT03043313) regimen, which demonstrated the clinical utility of combining trastuzumab (Herceptin) with tucatinib (Tukysa)—a small molecule HER2 inhibitor—for second-line treatment in patients with HER2-positive CRC, she explains. The MOUNTAINEER study established this regimen as an effective option in this setting, Parikh reports.

Additionally, another promising treatment involves fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), an antibody-drug conjugate with notable effectiveness in patients with high levels of HER2 amplification, as confirmed by fluorescence in situ hybridization or immunohistochemistry, she continues. For patients whose tumors are truly HER2 amplified, T-DXd is a viable treatment that can be administered following prior treatment with trastuzumab plus tucatinib, Parikh emphasizes. Furthermore, clinical data indicate that T-DXd remains effective even after previous HER2-targeted therapies, providing a valuable sequential option, she states.

When evaluating T-DXd in HER2-amplified CRC, it is essential to assess patient-specific factors, such as KRAS mutation status, Parikh expands. In cases where a patient has both HER2 amplification and a KRAS mutation, T-DXd might be used as an alternative to trastuzumab plus tucatinib, she notes, adding that it is rare for HER2-amplified CRC to harbor KRAS mutations. However, this subset of patients could benefit from T-DXd, either as a substitute for or sequentially after other HER2-targeted options, Parikh emphasizes. Overall, Parikh concludes by stating that for HER2-amplified CRC, the MOUNTAINEER regimen and T-DXd represent valuable treatment options, with the choice depending on HER2 amplification status, previous treatments, and possible KRAS mutation presence.