EvidenceHER2-amplified colorectal cancer

HER2 amplification testing is now standard in RAS wild-type metastatic colorectal cancer, and tucatinib-trastuzumab is the approved chemotherapy-free option after first-line therapy.

The first United States approval of a HER2-directed regimen in colorectal cancer, and the basis for MOUNTAINEER-03, which is testing the combination with chemotherapy in the first line.

Trastuzumab deruxtecan is an option for HER2-positive colorectal cancer after HER2 antibodies, and it contributed to the tumour-agnostic approval for HER2 3+ solid tumours; lung monitoring is essential.

The antibody-drug conjugate route into HER2-positive colorectal cancer, extended by DESTINY-CRC02 at a lower dose; interstitial lung disease is the class risk that defines how the drug is monitored.

The first demonstration that HER2 is actionable in colorectal cancer, and the trial that defined the colorectal-specific HER2 scoring criteria every later trial has used.

HERACLES opened HER2 as a target in colorectal cancer and set the immunohistochemistry and in situ hybridisation criteria later studies used; tucatinib and trastuzumab deruxtecan built on this result.

The paper that put HER2 on the colorectal map (HERACLES, MOUNTAINEER and DESTINY-CRC follow from it) and that showed the hypermutated group, later the immunotherapy-responsive group, is defined by two distinct mechanisms.