2022
Phase 2 trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ locally advanced or metastatic breast cancer with and without brain metastases (HER2CLIMB-04, trial in progress).
Krop I, Carey L, Ramos J, Chen Y, Hamilton E. Phase 2 trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ locally advanced or metastatic breast cancer with and without brain metastases (HER2CLIMB-04, trial in progress). Journal Of Clinical Oncology 2022, 40: tps1111-tps1111. DOI: 10.1200/jco.2022.40.16_suppl.tps1111.Peer-Reviewed Original ResearchHuman epidermal growth factor receptor 2Metastatic breast cancerDisease control rateProgression-free survivalDuration of responseBrain metastasesAntibody-drug conjugatesRECIST 1.1Trastuzumab deruxtecanInvestigator assessmentBreast cancerSmall molecule tyrosine kinase inhibitorsTopoisomerase I inhibitor payloadEpidermal growth factor receptor 2Monoclonal antibodiesBreast cancer xenograft modelActive brain metastasesResponse-evaluable patientsManageable safety profileObjective response ratePhase 2 studyPhase 2 trialGrowth factor receptor 2Limited treatment optionsPatient-reported outcomes
2021
FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036
Angus SP, Stuhlmiller TJ, Mehta G, Bevill SM, Goulet DR, Olivares-Quintero JF, East MP, Tanioka M, Zawistowski JS, Singh D, Sciaky N, Chen X, He X, Rashid NU, Chollet-Hinton L, Fan C, Soloway MG, Spears PA, Jefferys S, Parker JS, Gallagher KK, Forero-Torres A, Krop IE, Thompson AM, Murthy R, Gatza ML, Perou CM, Earp HS, Carey LA, Johnson GL. FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036. Npj Breast Cancer 2021, 7: 51. PMID: 33980863, PMCID: PMC8115531, DOI: 10.1038/s41523-021-00258-0.Peer-Reviewed Original ResearchHER2/ErbB2 receptorGene signatureAnti-HER2 monoclonal antibodyHER2-positive malignanciesImmune gene signaturesAnti-HER2 therapyHER2-positive breastPotential therapeutic strategyAnti-HER2 antibodyFOXA1 depletionHER3 levelsProliferation gene signatureClinical trialsPharmacodynamic responseBreast cancerImmune responseTherapeutic strategiesFOXA1 expressionTranscription factor FOXA1Cell line responseHER2Adaptive responseMonoclonal antibodiesAdaptive upregulationLapatinib
2013
Pertuzumab: Optimizing HER2 Blockade
Metzger-Filho O, Winer EP, Krop I. Pertuzumab: Optimizing HER2 Blockade. Clinical Cancer Research 2013, 19: 5552-5556. PMID: 23942091, DOI: 10.1158/1078-0432.ccr-13-0518.Peer-Reviewed Original ResearchConceptsBreast cancerAdvanced HER2-positive breast cancerHER2-positive breast cancerRecombinant humanized monoclonal antibodyAddition of pertuzumabTrastuzumab/pertuzumabPhase III studyProgression-free survivalFirst-line treatmentMetastatic breast cancerRisk of mortalityHumanized monoclonal antibodyHeterodimerization of HER2EGF receptorMechanism of actionHER2 blockadeIII studyClinical dataHER familyHER2-HER3 heterodimersPertuzumabDrug AdministrationMonoclonal antibodiesU.S. FoodHER2-HER3Beyond Trastuzumab and Lapatinib: New Options for HER2-Positive Breast Cancer
Zardavas D, Cameron D, Krop I, Piccart M. Beyond Trastuzumab and Lapatinib: New Options for HER2-Positive Breast Cancer. American Society Of Clinical Oncology Educational Book 2013, e2-e11. DOI: 10.14694/edbook_am.2013.33.e2.Peer-Reviewed Original ResearchHER2-positive breast cancerDual HER2 blockadeAntibody-drug conjugatesHER2 blockadeMetastatic settingBreast cancerAdjuvant settingTrastuzumab-DM1Clinical trialsSmall molecule inhibitorsClinical practiceMonoclonal antibodiesAnti-HER2 resistanceAnti-HER2 agentsLarge randomized trialsEfficacy of trastuzumabSubset of patientsAdvanced clinical testingHER2-targeted agentsNew treatment optionsAggressive biologic behaviorDrug conjugatesMajor clinical issueImproved treatment outcomesMolecule inhibitors
2009
Mechanisms of trastuzumab resistance in breast cancer.
Tolaney SM, Krop IE. Mechanisms of trastuzumab resistance in breast cancer. Anti-Cancer Agents In Medicinal Chemistry 2009, 9: 348-55. PMID: 19275526, DOI: 10.2174/1871520610909030348.Peer-Reviewed Original ResearchConceptsBreast cancerTrastuzumab resistanceHER2-positive metastatic breast cancerHER2-positive breast cancerDevelopment of trastuzumabOutcomes of patientsTrastuzumab-based therapyMetastatic breast cancerInvasive breast cancerHER2/neu geneHumanized monoclonal antibodyPoor patient outcomesNovel therapeutic agentsPatient outcomesTherapeutic agentsPatientsTrastuzumabCancerMonoclonal antibodiesAntitumor activityNeu genePotential mechanismsOutcomesSignificant improvementExtracellular domain