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The first trial to treat bowel cancer as a HER2 disease. Screening 914 patients to find 48 with extra HER2, it produced lasting responses in nearly a third of those treated, after every standard drug had failed.
HERACLES was a proof-of-concept, multicentre, open-label, phase 2 trial at four Italian academic cancer centres. Adults with KRAS exon 2 wild-type, HER2-positive metastatic colorectal cancer refractory to standard of care including an EGFR antibody received intravenous trastuzumab and oral lapatinib until progression, with HER2 positivity defined by the previously validated colorectal-specific criteria. Between August 2012 and May 2015, 914 KRAS exon 2 wild-type patients were screened and 48 (5%) had HER2-positive tumours; 27 were eligible and treated. At data cutoff with a median follow-up of 94 weeks, 8 of 27 (30%) had achieved an objective response, 1 complete and 7 partial, and 12 (44%) had stable disease. Six of 27 patients had grade 3 adverse events and there were no grade 4 or 5 events.
It established HER2 amplification as an actionable colorectal genotype and set the screening arithmetic every later HER2 trial has faced: you must test about 20 wild-type patients to find one eligible patient.
Shares Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Andrea Sartore-Bianchi, Salvatore Siena, HERACLES.
Shares Andrea Sartore-Bianchi, HERACLES, Lapatinib, The Lancet Oncology.
Shares HERACLES, Lapatinib, Istituto di Candiolo IRCCS (FPO), Receptor tyrosine kinase activation.
Shares Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Andrea Sartore-Bianchi, Salvatore Siena, Istituto di Candiolo IRCCS (FPO).
Shares Salvatore Siena, Lapatinib, The Lancet Oncology, Trastuzumab.
Shares HER2 ISH amplified (ERBB2 gene amplification), Receptor tyrosine kinase activation, The Lancet Oncology, HER2.
Shares HER2 ISH amplified (ERBB2 gene amplification), Receptor tyrosine kinase activation, The Lancet Oncology, Trastuzumab.
Shares HERACLES, HER2 ISH amplified (ERBB2 gene amplification), KRAS, HER2.