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Milan oncologist who co-led HERACLES and was lead author of DESTINY-CRC01, which showed trastuzumab deruxtecan is active in HER2-positive colorectal cancer, and a leader of the anti-EGFR antibody trials in the disease.
Salvatore Siena is professor of medical oncology at the University of Milan and led the Niguarda Cancer Center's oncology programme. He was a senior investigator of HERACLES and first author of the 2021 Lancet Oncology report of DESTINY-CRC01, the phase 2 trial in which trastuzumab deruxtecan produced responses in HER2-positive, RAS wild-type metastatic colorectal cancer after standard therapy. He was also a lead investigator of the panitumumab trials that established RAS testing before anti-EGFR treatment.
| Title | Journal | Year |
|---|---|---|
| DESTINY-CRC01: trastuzumab deruxtecan in HER2-expressing metastatic colorectal cancer | The Lancet Oncology | 2021 |
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.
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.
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.
Extended RAS testing (KRAS and NRAS exons 2, 3 and 4) became the standard before any EGFR antibody, and about one in six patients who would previously have been treated is now spared a drug that would have made things worse.
It made acquired resistance a measurable, plasma-readable event, and it is the origin of anti-EGFR rechallenge strategies guided by ctDNA clearance of the resistant clone.
Shares Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, HERACLES, Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer, Assessment of a HER2 scoring system for colorectal cancer: results from a validation study and the tags colorectal, targeted-therapy, trialist.
Shares Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER), HER2-amplified colorectal cancer, Colorectal cancer and the tags colorectal, targeted-therapy, trialist.
Shares Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer, Colorectal cancer and the tags colorectal, targeted-therapy, trialist.
Shares Colorectal cancer and the tags colorectal, trialist.
Shares Colorectal cancer and the tags colorectal, trialist.
Shares Colorectal cancer and the tags colorectal, trialist.
Shares Colorectal cancer and the tags colorectal, trialist.
Shares Colorectal cancer and the tags colorectal, trialist.