{"entity":{"id":"paper-heracles-trastuzumab-lapatinib-her2-colorectal-lancet-oncol-2016","kind":"paper","name":"Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES)","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-24","links":[{"label":"Sartore-Bianchi et al., Lancet Oncol 2016: HERACLES, trastuzumab plus lapatinib in HER2-positive metastatic colorectal cancer","url":"https://doi.org/10.1016/S1470-2045(16)00150-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27108243/"}],"tags":[],"related":["her2-ish-amplified"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["her2","kras"],"drugs":["trastuzumab","lapatinib"],"companies":[],"institutions":["niguarda-cancer-center","candiolo"],"pathways":["rtk-activation"],"terms":[],"trials":["heracles"],"people":["andrea-sartore-bianchi","salvatore-siena"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2016,"doi":"10.1016/S1470-2045(16)00150-9","pmid":"27108243","authors":"Sartore-Bianchi A, Trusolino L, Martino C, et al.","paperType":"rct","findings":["48 of 914 KRAS exon 2 wild-type patients (5%) were HER2-positive.","Objective response in 8 of 27 (30%), one complete; stable disease in 12 (44%).","No grade 4 or 5 adverse events."],"whatItMeans":"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.","caveats":["27 patients, single-arm, no randomised comparison.","KRAS exon 2 only; extended RAS was not required.","Trastuzumab plus lapatinib has since been superseded by tucatinib plus trastuzumab and by trastuzumab deruxtecan."],"changedPractice":true,"participants":27},"route":"/key-papers/paper-heracles-trastuzumab-lapatinib-her2-colorectal-lancet-oncol-2016/","neighbours":{"biomarker":[{"id":"her2-ish-amplified","kind":"biomarker","name":"HER2 ISH amplified (ERBB2 gene amplification)","route":"/biomarkers/her2-ish-amplified/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"drug":[{"id":"lapatinib","kind":"drug","name":"Lapatinib","route":"/drugs/lapatinib/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}],"institution":[{"id":"candiolo","kind":"institution","name":"Istituto di Candiolo IRCCS (FPO)","route":"/institutions/candiolo/"},{"id":"niguarda-cancer-center","kind":"institution","name":"Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda","route":"/institutions/niguarda-cancer-center/"}],"pathway":[{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"trial":[{"id":"heracles","kind":"trial","name":"HERACLES","route":"/trials/heracles/"}],"person":[{"id":"andrea-sartore-bianchi","kind":"person","name":"Andrea Sartore-Bianchi","route":"/people/andrea-sartore-bianchi/"},{"id":"salvatore-siena","kind":"person","name":"Salvatore Siena","route":"/people/salvatore-siena/"}],"journal":[{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","route":"/journals/lancet-oncology/"}]}}