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HERACLES showed that the breast cancer drugs trastuzumab and lapatinib, used together, could shrink bowel cancers that carry extra copies of the HER2 gene, turning a laboratory prediction into a treatment for this small group of patients.
Work in patient-derived xenografts had shown that HER2-amplified colorectal cancers respond to dual HER2 blockade. HERACLES was an Italian proof-of-concept phase 2 trial that screened KRAS wild-type metastatic colorectal cancers for HER2 amplification and treated those found, after failure of standard therapies including cetuximab or panitumumab, with trastuzumab plus lapatinib (cohort A). A second cohort tested pertuzumab with trastuzumab emtansine.
In cohort A roughly a third of the heavily pretreated patients had an objective response and responses lasted for many months, establishing HER2 amplification as an actionable target in colorectal cancer and setting up the later MyPathway, MOUNTAINEER and DESTINY-CRC trials.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
54 enrolled.
95% CI 14 to 50; median follow-up 94 weeks
SourceThe 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.
It fixes the population size for HER2-directed therapy, shows the enrichment in wild-type disease that makes reflex HER2 testing worthwhile there, and establishes that HER2 is not itself prognostic in this cancer.
It is the threshold behind the colorectal HER2 approvals: the more-than-50% rule, rather than the 10% used in gastric cancer, is what a pathologist applies when a bowel cancer is called HER2-positive.
It is where HER2-directed colorectal therapy came from: the xenopatient result led directly to HERACLES and therefore to every HER2 regimen now used in the disease.
Shares Pertuzumab, Trastuzumab, Monoclonal antibodies and the tag subtype-trials.
Shares Trastuzumab emtansine, Trastuzumab and the tag subtype-trials.
Shares Pertuzumab, Trastuzumab and the tag subtype-trials.
Shares Lapatinib, Trastuzumab and the tag subtype-trials.
Shares Lapatinib and the tag subtype-trials.
Shares Trastuzumab emtansine and the tag subtype-trials.
Shares Trastuzumab and the tag subtype-trials.
Shares Monoclonal antibodies and the tag subtype-trials.