biostudies-literatureGoh GCancer Research UKNovo Nordisk UK Research FoundationEU FP7RosetreesBreast Cancer Research FoundationRosetrees TrustEuropean Research CouncilMedical Research CouncilThe Francis Crick InstituteBoehringer IngelheimAgency for Science, Technology and ResearchNational Institute for Health Research (NIHR)Prostate Cancer FoundationNovo Nordisk FondenWellcome Truste1002136https://www.ebi.ac.uk/biostudies/studies/S-EPMC5140058biostudies-literatureUnknown13(12)<h4>Background</h4>Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy.<h4>Methods and findings</h4>HER2-positive IBC patients received afatinib 40 mg daily until progression, and thereafter afatinib 40 mg daily and intravenous vinorelbine 25 mg/m2 weekly. The primary endpoint was clinical benefit; secondaPLoS medicineClonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory Breast Cancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine.PMC514005817786M179FC001169NNF15OC00165841658419310259303G0701935M44510169M391Swanton CChitapanarux ISpector NGibson NHerrero JDechaphunkul ASchmid RYau TUttenreuther-Fischer MGuiver KGanju VKim SBArpornwirat WGoh GAhmed SBJohnston SRIm SAAfrit MManeechavakajorn JfalseClonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory Breast Cancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine.<h4>Background</h4>Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy.<h4>Methods and findings</h4>HER2-positive IBC patients received afatinib 40 mg daily until progression, and thereafter afatinib 40 mg daily and intravenous vinorelbine 25 mg/m2 weekly. The primary endpoint was clinical benefit; seconda2016-01-01T00:00:00Z2016 Dec2026-04-29T04:46:51.933Z2019-03-26T22:48:59ZS-EPMC51400582792304310.1371/journal.pmed.1002136