2024
The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results
Lewis G, Li G, Guo J, Yu S, Fields C, Lee G, Zhang D, Dragovich P, Pillow T, Wei B, Sadowsky J, Leipold D, Wilson T, Kamath A, Mamounas M, Lee M, Saad O, Choeurng V, Ungewickell A, Monemi S, Crocker L, Kalinsky K, Modi S, Jung K, Hamilton E, LoRusso P, Krop I, Schutten M, Commerford R, Sliwkowski M, Cho E. The HER2-directed antibody-drug conjugate DHES0815A in advanced and/or metastatic breast cancer: preclinical characterization and phase 1 trial results. Nature Communications 2024, 15: 466. PMID: 38212321, PMCID: PMC10784567, DOI: 10.1038/s41467-023-44533-z.Peer-Reviewed Original ResearchConceptsHER2 antibody-drug conjugatesAntibody-drug conjugatesMetastatic breast cancerPhase 1 trialBreast cancerHER2-positive metastatic breast cancerHER2-positive breast cancerObjective response rateDose-escalation studyDuration of responseModel of HER2Anti-tumor activityMechanism of actionTrastuzumab deruxtecanPulmonary toxicityTrastuzumab emtansinePreclinical characterizationResponse rateHigh dosesVivo efficacySecondary objectiveEarly signsPotent cytotoxic agentCytotoxic agentsCancer
2021
Phase II Single-Arm Study to Assess Trastuzumab and Vinorelbine in Advanced Breast Cancer Patients With HER2-Negative Tumors and HER2-Positive Circulating Tumor Cells
Parsons HA, Macrae ER, Guo H, Li T, Barry WT, Tayob N, Wulf GM, Isakoff SJ, Krop IE. Phase II Single-Arm Study to Assess Trastuzumab and Vinorelbine in Advanced Breast Cancer Patients With HER2-Negative Tumors and HER2-Positive Circulating Tumor Cells. JCO Precision Oncology 2021, 5: 896-903. PMID: 34994617, PMCID: PMC9848583, DOI: 10.1200/po.20.00461.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerHER2-positive CTCsHER2-negative metastatic breast cancerObjective response rateBreast cancerHER2-Positive Circulating Tumor CellsHER2-positive metastatic breast cancerResponse rateMedian progression-free survivalPhase II single-arm studyProgressive metastatic breast cancerHER2-negative breast cancerAdvanced breast cancer patientsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Tumor cellsHER2-positive diseasePrior chemotherapy regimenTumor tissue testingClinical benefit ratePrimary end pointPhase II trialProgression-free survivalGrowth factor receptor 2HER2-negative tumors
2019
HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade
Prat A, Pascual T, De Angelis C, Gutierrez C, Llombart-Cussac A, Wang T, Cortés J, Rexer B, Paré L, Forero A, Wolff AC, Morales S, Adamo B, Brasó-Maristany F, Vidal M, Veeraraghavan J, Krop I, Galván P, Pavlick AC, Bermejo B, Izquierdo M, Rodrik-Outmezguine V, Reis-Filho JS, Hilsenbeck SG, Oliveira M, Dieci MV, Griguolo G, Fasani R, Nuciforo P, Parker JS, Conte P, Schiff R, Guarneri V, Osborne CK, Rimawi MF. HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade. Journal Of The National Cancer Institute 2019, 112: 46-54. PMID: 31037288, PMCID: PMC7850037, DOI: 10.1093/jnci/djz042.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicFemaleGene ExpressionHumansLapatinibMiddle AgedMolecular Targeted TherapyNeoadjuvant TherapyNeoplasm StagingPrognosisReceptor, ErbB-2Reproducibility of ResultsSurvival AnalysisTreatment OutcomeConceptsHER2-positive breast cancerProgression-free survivalOverall response rateHER2-positive diseasePathological complete responseOverall survivalBreast cancerEarly diseaseAdvanced HER2-positive diseaseLonger progression-free survivalHigher overall response rateDual HER2 blockadeLonger overall survivalHER2-positive tumorsHER2 blockadeNeoadjuvant lapatinibNeoadjuvant trastuzumabAdvanced diseaseComplete responsePrimary outcomeClinical trialsIntrinsic subtypesIdentifies tumorsAdvanced settingERBB2 mRNA
2018
Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: ASCO Clinical Practice Guideline Update
Giordano SH, Temin S, Chandarlapaty S, Crews JR, Esteva FJ, Kirshner JJ, Krop IE, Levinson J, Lin NU, Modi S, Patt DA, Perlmutter J, Ramakrishna N, Winer EP, Davidson NE. Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: ASCO Clinical Practice Guideline Update. Journal Of Clinical Oncology 2018, 36: jco.2018.79.269. PMID: 29939838, DOI: 10.1200/jco.2018.79.2697.Peer-Reviewed Original ResearchConceptsAdvanced breast cancerBreast cancerSystemic therapyTrastuzumab emtansineEstrogen receptor-positive/progesterone receptor-positive breast cancerAdvanced human epidermal growth factor receptorASCO Clinical Practice Guideline UpdateHER2-positive advanced breast cancerProgesterone receptor-positive breast cancerClinical congestive heart failureClinical Practice Guideline UpdateEvidence-based guideline recommendationsStandard first-line therapyPositive advanced breast cancerLeft ventricular ejection fractionReceptor-positive breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Human epidermal growth factor receptorThird-line settingSecond-line treatmentFirst-line therapyFirst-line treatmentProgression-free survivalTime of progressionPhase 1/1b dose escalation and expansion study of BEZ235, a dual PI3K/mTOR inhibitor, in patients with advanced solid tumors including patients with advanced breast cancer
Rodon J, Pérez-Fidalgo A, Krop IE, Burris H, Guerrero-Zotano A, Britten CD, Becerra C, Schellens J, Richards DA, Schuler M, Abu-Khalaf M, Johnson FM, Ranson M, Edenfield J, Silva AP, Hackl W, Quadt C, Demanse D, Duval V, Baselga J. Phase 1/1b dose escalation and expansion study of BEZ235, a dual PI3K/mTOR inhibitor, in patients with advanced solid tumors including patients with advanced breast cancer. Cancer Chemotherapy And Pharmacology 2018, 82: 285-298. PMID: 29882016, PMCID: PMC6286256, DOI: 10.1007/s00280-018-3610-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDose-Response Relationship, DrugDrug CompoundingFemaleHumansImidazolesMaleMiddle AgedNeoplasmsPhosphoinositide-3 Kinase InhibitorsQuinolinesTOR Serine-Threonine KinasesTrastuzumabConceptsAdvanced breast cancerSingle agentBreast cancerSolid tumorsHigh dosesPhase I/IbEnd pointDual PI3K/mTOR inhibitorContinuous daily scheduleDose-escalation partMost frequent AEsOpen-label studyPrimary end pointSecondary end pointsAdvanced solid tumorsPI3K/mTOR inhibitorCombination cohortConclusionsThe MTDGastrointestinal AEsPartial responseDose escalationFrequent AEsOral inhibitorResultsOne hundredLow doseObesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2
Incio J, Ligibel JA, McManus DT, Suboj P, Jung K, Kawaguchi K, Pinter M, Babykutty S, Chin SM, Vardam TD, Huang Y, Rahbari NN, Roberge S, Wang D, Gomes-Santos IL, Puchner SB, Schlett CL, Hoffmman U, Ancukiewicz M, Tolaney SM, Krop IE, Duda DG, Boucher Y, Fukumura D, Jain RK. Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2. Science Translational Medicine 2018, 10 PMID: 29540614, PMCID: PMC5936748, DOI: 10.1126/scitranslmed.aag0945.Peer-Reviewed Original ResearchConceptsVEGF therapyInterleukin-6Breast cancerMouse modelAnti-vascular endothelial growth factor therapyEndothelial growth factor therapyTumor vasculatureAnti-VEGF therapyAnti-VEGF treatmentIL-6 blockadeGrowth factor therapyIL-6 productionFGF-2Up-regulates IL-6Second mouse modelFGF-2 expressionTumor cell proliferationFactor therapyGrowth factor 2Proinflammatory factorsMetastatic sitesBC patientsObese miceReceptor inhibitionSystemic concentrations
2017
Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial
Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop IE, Blackwell K, Hoersch S, Xu J, Green M, Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. The Lancet Oncology 2017, 18: 732-742. PMID: 28526536, PMCID: PMC5531181, DOI: 10.1016/s1470-2045(17)30312-1.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAged, 80 and overAnemiaAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsAspartate AminotransferasesBreast NeoplasmsBreast Neoplasms, MaleBridged-Ring CompoundsCapecitabineDiarrheaDisease-Free SurvivalFemaleHand-Foot SyndromeHumansLapatinibMaleMaytansineMiddle AgedQuinazolinesReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsRetreatmentSurvival RateTaxoidsThrombocytopeniaTrastuzumabVomitingYoung AdultConceptsWorse adverse eventsMetastatic breast cancerHER2-positive metastatic breast cancerInterim overall survival analysisProgression-free survivalOverall survival dataTrastuzumab emtansineOverall survivalAdverse eventsOverall survival analysisBreast cancerGrade 3Safety profileHER2-positive advanced breast cancerSurvival analysisFinal overall survival dataFinal overall survival resultsPalmar-plantar erythrodysaesthesia syndromeCoprimary efficacy endpointsFinal overall survivalPrevious chemotherapy regimensMedian overall survivalAdvanced breast cancerPhase 3 trialStudy drug discontinuationTrastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial
Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic T, Hoersch S, Smitt M, Wildiers H. Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. The Lancet Oncology 2017, 18: 743-754. PMID: 28526538, DOI: 10.1016/s1470-2045(17)30313-3.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsBreast Neoplasms, MaleBridged-Ring CompoundsChemotherapy-Induced Febrile NeutropeniaDiarrheaEarly Termination of Clinical TrialsFemaleHemorrhageHumansLapatinibMaleMaytansineMiddle AgedNeoplasm MetastasisNeutropeniaPractice Patterns, Physicians'QuinazolinesReceptor, ErbB-2RetreatmentSurvival RateTaxoidsThrombocytopeniaTrastuzumabConceptsHER2-positive advanced breast cancerPhysician's choice groupAdvanced breast cancerWorse adverse eventsProgression-free survivalOverall survivalTrastuzumab emtansineAdverse eventsOverall survival analysisBreast cancerPhysician's choiceTH3RESA trialGrade 3Eastern Cooperative Oncology Group performance statusInvestigator-assessed progression-free survivalOpen-label phase 3 trialHER2-positive metastatic breast cancerSurvival analysisFinal overall survival analysisFinal overall survival resultsAdequate organ functionCommon grade 3Permuted block randomisationTrastuzumab emtansine treatmentSecond interim analysis
2016
3rd ESO–ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3)
Cardoso F, Costa A, Senkus E, Aapro M, André F, Barrios C, Bergh J, Bhattacharyya G, Biganzoli L, Cardoso M, Carey L, Corneliussen-James D, Curigliano G, Dieras V, Saghir N, Eniu A, Fallowfield L, Fenech D, Francis P, Gelmon K, Gennari A, Harbeck N, Hudis C, Kaufman B, Krop I, Mayer M, Meijer H, Mertz S, Ohno S, Pagani O, Papadopoulos E, Peccatori F, Pernault-Llorca F, Piccart M, Pierga J, Rugo H, Shockney L, Sledge G, Swain S, Thomssen C, Tutt A, Vorobiof D, Xu B, Norton L, Winer E. 3rd ESO–ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3). The Breast 2016, 31: 244-259. PMID: 27927580, DOI: 10.1016/j.breast.2016.10.001.Peer-Reviewed Original ResearchCombination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases
Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nature Medicine 2016, 22: 723-726. PMID: 27270588, PMCID: PMC4938731, DOI: 10.1038/nm.4120.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAminopyridinesAnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsBreast NeoplasmsCarrier ProteinsCaspase 3Cell Cycle ProteinsDNA RepairDrug Resistance, NeoplasmDrug Therapy, CombinationEukaryotic Initiation FactorsEverolimusFemaleGene Expression ProfilingGenomic InstabilityHumansImmunohistochemistryKi-67 AntigenMagnetic Resonance ImagingMechanistic Target of Rapamycin Complex 1MiceMice, SCIDMolecular Targeted TherapyMorpholinesMultiprotein ComplexesNeoplasm TransplantationPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationReceptor, ErbB-2Remission InductionTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesCancer brain metastasesBrain metastasesHER2-positive breast cancer brain metastasesOrthotopic patient-derived xenograftsPI3KPatient-derived xenograftsDurable remissionsTherapeutic responseMouse modelCombined inhibitionCombination inhibitionMetastasisInhibitionRemissionXenograftsMiceLessons from breast cancer trials of HER2-kinase inhibitors
Krop IE. Lessons from breast cancer trials of HER2-kinase inhibitors. The Lancet Oncology 2016, 17: 267-268. PMID: 26822399, DOI: 10.1016/s1470-2045(16)00004-8.Peer-Reviewed Original Research
2015
The Evolving Landscape of HER2 Targeting in Breast Cancer
Moasser MM, Krop IE. The Evolving Landscape of HER2 Targeting in Breast Cancer. JAMA Oncology 2015, 1: 1154. PMID: 26204261, DOI: 10.1001/jamaoncol.2015.2286.Peer-Reviewed Original ResearchConceptsTreatment of HER2Breast cancerImmunologic effectorsHER2 targetingSubstantial single-agent activityHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Value of HER2Lines of therapyGrowth factor receptor 2Single-agent activityLate-stage diseaseStage of diseaseUseful predictive biomarkerHER2 inhibitor lapatinibFactor receptor 2Variety of cytotoxicModest efficacyTrastuzumab resistancePredictive biomarkersCell surface expressionImmunologic activityInhibitor lapatinibReceptor 2Advanced stageTrastuzumab Emtansine (T-DM1) in Patients With HER2-Positive Metastatic Breast Cancer Previously Treated With Chemotherapy and 2 or More HER2-Targeted Agents
Yardley DA, Krop IE, LoRusso PM, Mayer M, Barnett B, Yoo B, Perez EA. Trastuzumab Emtansine (T-DM1) in Patients With HER2-Positive Metastatic Breast Cancer Previously Treated With Chemotherapy and 2 or More HER2-Targeted Agents. The Cancer Journal 2015, 21: 357-364. PMID: 26389758, DOI: 10.1097/ppo.0000000000000144.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsBreast Neoplasms, MaleComorbidityFemaleHumansMaleMaytansineMiddle AgedMolecular Targeted TherapyNeoplasm MetastasisNeoplasm Recurrence, LocalNeoplasm StagingReceptor, ErbB-2RetreatmentTrastuzumabTreatment OutcomeConceptsMetastatic breast cancerObjective response rateAdvanced breast cancerBreast cancerT-DM1Measurable diseaseAdverse eventsTrastuzumab emtansineGrade 3Investigator-assessed objective response rateHER2-positive metastatic breast cancerResponse ratePositive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Grade adverse eventsNew safety signalsPhase III studyGrowth factor receptor 2Significant cardiovascular diseaseVentricular ejection fractionPlatelet count decreaseSimilar patient populationsRoutine clinical practiceFactor receptor 2Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer
Tolaney SM, Tan S, Guo H, Barry W, Van Allen E, Wagle N, Brock J, Larrabee K, Paweletz C, Ivanova E, Janne P, Overmoyer B, Wright JJ, Shapiro GI, Winer EP, Krop IE. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer. Investigational New Drugs 2015, 33: 1108-1114. PMID: 26123926, PMCID: PMC4608248, DOI: 10.1007/s10637-015-0269-8.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerPhase 2 studyProgression-free survivalBreast cancerPartial responseSingle-arm phase 2 studyResults 22 patientsPhase II studyDaily oral dosingOverall response rateRecent preclinical dataMechanism of actionTivantinib monotherapyMetastatic settingAdverse eventsII studyMethods PatientsPrior linesPreclinical dataOral dosingTivantinibPatientsMET expressionResponse rate
2014
Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA †
Krop IE, Lin NU, Blackwell K, Guardino E, Huober J, Lu M, Miles D, Samant M, Welslau M, Diéras V. Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA †. Annals Of Oncology 2014, 26: 113-119. PMID: 25355722, PMCID: PMC4679405, DOI: 10.1093/annonc/mdu486.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntimetabolites, AntineoplasticAntineoplastic AgentsBreast NeoplasmsCapecitabineCentral Nervous System NeoplasmsDeoxycytidineDisease-Free SurvivalFemaleFluorouracilHumansLapatinibMaytansineMiddle AgedQuinazolinesReceptor, ErbB-2Retrospective StudiesTrastuzumabYoung AdultConceptsCentral nervous system metastasesAsymptomatic CNS metastasesCNS metastasesNervous system metastasesAdvanced breast cancerT-DM1CNS metastasisOverall survivalBreast cancerTrastuzumab emtansineHER2-positive advanced breast cancerHER2-positive metastatic breast cancerPositive advanced breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2T-DM1 armNew safety signalsProgression-free survivalGrowth factor receptor 2Metastatic breast cancerFactor receptor 2Independent reviewCNS progressionEMILIA studyAdverse eventsSeeds and Soil: Unraveling the Role of Local Tumor Stroma in Distant Metastasis
Duda DG, Ancukiewicz M, Isakoff SJ, Krop IE, Jain RK. Seeds and Soil: Unraveling the Role of Local Tumor Stroma in Distant Metastasis. Journal Of The National Cancer Institute 2014, 106: dju187. PMID: 25082335, DOI: 10.1093/jnci/dju187.Peer-Reviewed Original ResearchTrastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: An Integrated Safety Analysis
Diéras V, Harbeck N, Budd GT, Greenson JK, Guardino AE, Samant M, Chernyukhin N, Smitt MC, Krop IE. Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: An Integrated Safety Analysis. Journal Of Clinical Oncology 2014, 32: 2750-2757. PMID: 25024070, DOI: 10.1200/jco.2013.54.4999.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerHER2-positive metastatic breast cancerHuman epidermal growth factor receptor 2Adverse eventsDrug discontinuationSafety profileT-DM1Trastuzumab emtansineBreast cancerGrade 3Dose reductionEpidermal growth factor receptor 2Human epidermal growth factor receptorCommon grade 3Grade adverse eventsRandomized phase IISelect adverse eventsBreast cancer settingGreater adverse eventsGrowth factor receptor 2Single-arm studyT-DM1 treatmentFavorable safety profileFactor receptor 2Epidermal growth factor receptorTrastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial
Krop IE, Kim SB, González-Martín A, LoRusso PM, Ferrero JM, Smitt M, Yu R, Leung AC, Wildiers H, collaborators O. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. The Lancet Oncology 2014, 15: 689-699. PMID: 24793816, DOI: 10.1016/s1470-2045(14)70178-0.Peer-Reviewed Original ResearchConceptsHER2-positive advanced breast cancerPhysician's choice groupWorse adverse eventsAdvanced breast cancerProgression-free survivalInterim overall survival analysisPhase 3 trialTrastuzumab emtansineAdverse eventsOverall survival analysisBreast cancerPhysician's choiceGrade 3Investigator-assessed progression-free survivalSurvival analysisBlock randomisation schemeCytotoxic agent DM1Previous taxane therapySerious adverse eventsWeb response systemMetastatic breast cancerEffective therapeutic optionPopulation of patientsFinal PFS analysisChoice groupNew research on the treatment of small HER2-positive breast cancers.
Krop IE. New research on the treatment of small HER2-positive breast cancers. Clinical Advances In Hematology And Oncology 2014, 12: 124-7. PMID: 24892258.Peer-Reviewed Original ResearchTrastuzumab Emtansine: A Novel Antibody–Drug Conjugate for HER2-Positive Breast Cancer
Krop I, Winer EP. Trastuzumab Emtansine: A Novel Antibody–Drug Conjugate for HER2-Positive Breast Cancer. Clinical Cancer Research 2014, 20: 15-20. PMID: 24135146, DOI: 10.1158/1078-0432.ccr-13-0541.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerT-DM1Breast cancerAntibody-drug conjugatesAntibody-dependent cell-mediated cytotoxicityRecent phase III trialsHER2-positive breast cancerNovel antibody-drug conjugateCapecitabine/lapatinibFirst-line settingHepatic transaminase elevationsCombination of trastuzumabPhase II studyProgression-free survivalPhase III trialsInhibition of HER2Cell-mediated cytotoxicityFavorable toxicity profileHER2-positive tumor cellsMonoclonal antibody trastuzumabTransaminase elevationII studyIII trialsOverall survivalAdverse events