HERACLES: trastuzumab and lapatinib in HER2-amplified, KRAS wild-type metastatic colorectal cancer
This small Italian trial was the first to show that HER2-amplified colorectal cancer responds to dual HER2 blockade, establishing HER2 as a genuine drug target in a disease where it had been ignored.
Overview
Proof-of-concept phase 2 trial that screened 914 KRAS exon 2 wild-type colorectal cancers to find 48 with HER2 amplification and treated 27 heavily pretreated patients with trastuzumab and lapatinib.
Objective response was 30 percent including one complete response, with disease control in 59 percent and a median progression-free survival of 21 weeks; the trial also defined the HERACLES diagnostic criteria for HER2 positivity in colorectal cancer.
- Objective response 30 percent (8 of 27), disease control 59 percent.
- HER2 amplification found in about 5 percent of KRAS wild-type tumours.
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.
- Very small and non-randomised.
- Lapatinib-based regimens have been superseded.
Similar pages
not linked directly; found by shared links- Key paperMOUNTAINEER: tucatinib plus trastuzumab for HER2-positive, RAS wild-type metastatic colorectal cancer
Shares HER2-amplified colorectal cancer, The Lancet Oncology, Trastuzumab.
- Key paperDESTINY-CRC01: trastuzumab deruxtecan in HER2-expressing metastatic colorectal cancer
Shares HER2-amplified colorectal cancer, The Lancet Oncology, Trastuzumab.
- TrialTL938 and Trastuzumab for Patients With HER2-positive Metastatic Colorectal Cancer
- TrialGeparSixto
Shares Lapatinib, Trastuzumab.
- TechnologyHER2 tyrosine kinase inhibitors
- TrialBeamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People Wit
- TrialMOUNTAINEER & MOUNTAINEER-03
- TrialMyPathway