Aparna Parikh, MD, highlighted the clinical utility of trastuzumab in combination with tucatinib, and fam-trastuzumab deruxtecan-nxki (T-DXd) as effective treatment options for patients with HER2-positive colorectal cancer (CRC). These targeted therapies offer valuable strategies for managing this subset of CRC, with treatment decisions guided by HER2 amplification status, prior treatments, and the presence of KRAS mutations.
MOUNTAINEER Trial: Trastuzumab and Tucatinib
The phase 2 MOUNTAINEER trial (NCT03043313) established the combination of trastuzumab (Herceptin) and tucatinib (Tukysa) as an effective second-line treatment for patients with HER2-positive CRC. Tucatinib, a small molecule HER2 inhibitor, enhances the efficacy of trastuzumab in this setting. According to Dr. Parikh, the MOUNTAINEER study has set a new standard for treating HER2-positive CRC.
Fam-Trastuzumab Deruxtecan-nxki (T-DXd) Efficacy
Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) is an antibody-drug conjugate that has demonstrated notable effectiveness in patients with high levels of HER2 amplification, confirmed by fluorescence in situ hybridization or immunohistochemistry. Dr. Parikh noted that T-DXd is a viable treatment option for patients whose tumors are truly HER2 amplified, even after prior treatment with trastuzumab plus tucatinib, providing a valuable sequential option.
Patient-Specific Factors: KRAS Mutation Status
When considering T-DXd in HER2-amplified CRC, assessing patient-specific factors such as KRAS mutation status is essential. Although rare, patients with both HER2 amplification and a KRAS mutation might benefit from T-DXd as an alternative to trastuzumab plus tucatinib, or sequentially after other HER2-targeted options. Dr. Parikh emphasized that the choice between the MOUNTAINEER regimen and T-DXd depends on HER2 amplification status, previous treatments, and the possible presence of KRAS mutations.
In summary, 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.
