Expert Insights into Testing and Treatment for HER2-Positive Metastatic Colorectal Cancer (mCRC)

Stacy A. Cohen, MD, provides an overview of colorectal cancer, noting increasing incidence in younger patients; Christina S. Wu, MB, BCh, MD, discussed possible reasons for more colorectal cancer in younger people, including genetic predisposition and exposures, though the causes remain unclear.

Drs Ahn and Cohen discuss the treatment of colorectal cancer, reviewing the available options and describing factors influencing treatment choice and use of maintenance therapy after initial response.

Drs Wu, Ciombor, and Cohen discussed upfront molecular testing in patients with colorectal cancer to guide treatment, with Dr Ciombor reviewing HER2 testing methods and Dr Cohen noting liquid biopsy limitations.

Drs Cohen, Wu, and Ahn discuss HER2 in colorectal cancer, explaining that increased expression indicates possible benefit from HER2 inhibitors; Ahn summarized studies showing modest activity of dual HER2 inhibition compared to single agent trastuzumab.

New treatment updates could help find more patient subtypes to target and treat in the world of CRC, according to Kristen K. Ciombor, MD, MSCI.

Christina S. Wu, MB, BCh, MD, presents the case of a 50-year-old man with metastatic colorectal cancer to the panel for discussion.

In the Phase 2 MOUNTAINEER-01 study of patients with HER2-positive metastatic colorectal cancer who were chemo-refractory, the combination of tucatinib and trastuzumab showed an impressive response rate and disease control rate, and median duration of response up to 12 months; Dr. Ahn notes these results compare favorably to prior studies of dual HER2 inhibition, with MOUNTAINEER-01 showing higher response rates.

Toxicities with tucatinib in patients with colorectal cancer like fatigue and GI issues are generally manageable but still require close monitoring, with early optimization of diarrhea management being key to allow patients to stay on effective treatment long-term.

Kristen K. Ciombor, MD, discussed the ongoing MOUNTAINEER-03 trial, a global Phase 3 study randomizing patients with untreated HER2-positive colorectal cancer patients to FOLFOX plus tucatinib/trastuzumab versus standard chemotherapy plus a biologic, which she said highlights the importance of upfront molecular testing and could change treatment.

Tanios S. Bekaii-Saab, MD, presents the case of a 64-year-old woman with HER2+ colorectal cancer to the panel for discussion.

Dr Stacy A. Cohen discusses the DESTINY-CRC01 trial investigating trastuzumab deruxtecan in patients with colorectal cancer, specifically addressing the use of a targeted therapy for HER2 in colorectal cancer patients, highlighting the importance of prior therapy history and optimal dosage to balance efficacy and toxicity.

Experts explore the management of interstitial lung disease in patients with colorectal cancer receiving treatment with trastuzumab deruxtecan and the consideration of liquid biopsies to assess HER2 status and adapt treatment strategies.

The panel reviews treatment strategies for HER2-positive metastatic colorectal cancer patients in various scenarios, including those with HER2 mutations, RAS mutations, and different levels of HER2 expression, emphasizing the importance of reprofiling and considering the duration of response before changing treatment approaches.

Drs Ciombor and Ahn discuss emerging HER2-targeted therapies in colorectal cancer, including antibody-drug conjugates and novel antibodies.

The panelists close by emphasizing key takeaways regarding the management of HER2+ colorectal cancer, including early molecular profiling to enable targeted therapy sequencing, assessing HER2 amplification level, and having a strategic plan upfront mapping out potential targeted therapy options rather than just starting chemotherapy.

Kristen K. Ciombor, MD, MSCI, gives an overview of the current treatment landscape for patients with metastatic colorectal cancer.