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For HER2-positive metastatic colorectal cancer, experts say tucatinib plus trastuzumab should come before T-DXd — and community practice often gets it backwards. A panel of GI oncologists highlighted testing gaps, sequencing rationale, and a pipeline of emerging agents that could reshape first-line care.
For patients with HER2-positive metastatic colorectal cancer (mCRC), a panel of GI oncologists reached a clear consensus: tucatinib plus trastuzumab should be used before T-DXd (trastuzumab deruxtecan). The reasoning? Durability. In the MOUNTAINEER trial, tucatinib plus trastuzumab delivered a median duration of response of 15.2 months, compared to just 7.0 months with T-DXd in DESTINY-CRC01 — and T-DXd carries a risk of serious lung toxicity. Yet in community settings, the order is often reversed, largely because generalist oncologists are more familiar with T-DXd from breast cancer treatment.
Testing gaps are another major hurdle. Experts noted that roughly 30% of community patients never get HER2 tested at all, and insurance delays can slow NGS results. Reflex IHC paired with ctDNA assays was flagged as the fastest path to a first-line treatment decision.
Key Takeaways:
Why it matters: With multiple HER2-directed options now available, getting the sequence right — and finding eligible patients early — could meaningfully extend survival in a population with limited options.
