2022
Six-year absolute invasive disease-free survival benefit of adding adjuvant pertuzumab to trastuzumab and chemotherapy for patients with early HER2-positive breast cancer: A Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY (BIG 4-11) trial
Gelber RD, Wang XV, Cole BF, Cameron D, Cardoso F, Tjan-Heijnen V, Krop I, Loi S, Salgado R, Kiermaier A, Frank E, Fumagalli D, Caballero C, de Azambuja E, Procter M, Clark E, Restuccia E, Heeson S, Bines J, Loibl S, Piccart-Gebhart M, Committee and Investigators A. Six-year absolute invasive disease-free survival benefit of adding adjuvant pertuzumab to trastuzumab and chemotherapy for patients with early HER2-positive breast cancer: A Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY (BIG 4-11) trial. European Journal Of Cancer 2022, 166: 219-228. PMID: 35313167, DOI: 10.1016/j.ejca.2022.01.031.Peer-Reviewed Original ResearchConceptsSubpopulation treatment effect pattern plotInvasive disease-free survivalComposite risk scoreAdjuvant pertuzumabAPHINITY trialTIL percentageBreast cancerRisk scoreSubpopulation treatment effect pattern plot analysisEarly HER2-positive breast cancerDisease-free survival benefitHER2-positive breast cancerTreatment effectsNode-positive cohortDisease-free survivalEarly breast cancerNodal statusSurvival benefitLymphocyte percentagePatient subpopulationsComposite riskPatientsCovariates of interestChemotherapyPertuzumab
2021
Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis
Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey L, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Feng W, Winer E. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Annals Of Oncology 2021, 33: 321-329. PMID: 34954044, DOI: 10.1016/j.annonc.2021.12.005.Peer-Reviewed Original ResearchConceptsProgression-free survivalMetastatic breast cancerPlacebo-combination groupOverall survivalCombination groupBreast cancerHER2CLIMB trialBrain metastasesMedian durationSafety outcomesPrimary analysisFinal overall survival analysisHuman epidermal growth factor receptor 2 positive metastatic breast cancerPositive metastatic breast cancerMeaningful survival benefitMedian overall survivalPlacebo-controlled trialOverall study populationOverall survival analysisFinal OSMetastatic HER2Placebo combinationAdverse eventsLast patientPrespecified subgroupsTrastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study
Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study. Journal Of Clinical Oncology 2021, 40: 438-448. PMID: 34890214, PMCID: PMC8824393, DOI: 10.1200/jco.21.00896.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalOverall populationTrastuzumab emtansineHigh-risk human epidermal growth factor receptorHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Early breast cancer treatmentHuman epidermal growth factor receptorAnthracycline-based chemotherapyCoprimary end pointsPrimary end pointDisease-free survivalSerious adverse eventsEarly breast cancerGlobal health statusGrowth factor receptor 2Treatment completion ratesStandard of careBreast cancer treatmentFactor receptor 2Epidermal growth factor receptorGrowth factor receptorEndocrine therapyAdverse eventsAlliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer
O'Sullivan CC, Ballman KV, McCall L, Kommalapati A, Zemla T, Weiss A, Mitchell M, Blinder V, Tung NM, Irvin WJ, Lee M, Goetz MP, Symmans WF, Borges VF, Krop I, Carey LA, Partridge AH. Alliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer. Future Oncology 2021, 17: 4665-4676. PMID: 34636255, PMCID: PMC8600597, DOI: 10.2217/fon-2021-0753.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsBreastBreast NeoplasmsChemoradiotherapy, AdjuvantChemotherapy, AdjuvantClinical Trials, Phase III as TopicDisease-Free SurvivalDouble-Blind MethodFemaleFollow-Up StudiesHumansMastectomyMiddle AgedMulticenter Studies as TopicNeoadjuvant TherapyNeoplasm Recurrence, LocalNeoplasm, ResidualOxazolesPlacebosProspective StudiesPyridinesQuinazolinesRandomized Controlled Trials as TopicReceptor, ErbB-2ConceptsInvasive disease-free survivalDisease-free survivalBrain metastasis-free survivalBreast cancer-free survivalDistant recurrence-free survivalT-DM1Overall survivalResidual diseaseHER2-positive invasive breast cancerAdjuvant T-DM1Cancer-free survivalRecurrence-free survivalInvasive breast cancerMetastasis-free survivalPharmacokinetic end pointsOutcomes of interestQuality of lifeEligible patientsAdjuvant radiotherapyEndocrine therapyNeoadjuvant chemotherapyCorrelative biomarkersCare guidelinesBreast cancerPlaceboAdjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial
Tolaney SM, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Briccetti F, Schneider B, Garrett AM, Marcom K, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu M, Ruddy K, Zheng Y, Rosenberg SM, Gelber RD, Trippa L, Barry W, DeMeo M, Burstein H, Partridge A, Winer EP, Krop I. Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial. Journal Of Clinical Oncology 2021, 39: 2375-2385. PMID: 34077270, DOI: 10.1200/jco.20.03398.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalT-DM1Breast cancerStage IStage I HER2-positive breast cancerHER2-positive breast cancerHuman epidermal growth factor receptorAdjuvant T-DM1Co-primary objectivesDisease-free survivalPatient-reported outcomesEpidermal growth factor receptorGrowth factor receptorProtocol therapyAnalysis populationTrastuzumab emtansineClinical trialsRelevant toxicityPatientsFactor receptorLess toxicityWeeksTrastuzumabCancerPaclitaxel
2020
Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis
Brastianos PK, Lee EQ, Cohen JV, Tolaney SM, Lin NU, Wang N, Chukwueke U, White MD, Nayyar N, Kim A, Alvarez-Breckenridge C, Krop I, Mahar MK, Bertalan MS, Shaw B, Mora JL, Goss N, Subramanian M, Nayak L, Dietrich J, Forst DA, Nahed BV, Batchelor TT, Shih HA, Gerstner ER, Moy B, Lawrence D, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Nature Medicine 2020, 26: 1280-1284. PMID: 32483359, DOI: 10.1038/s41591-020-0918-0.Peer-Reviewed Original ResearchConceptsPrimary endpointOpen-label phase 2 trialDose of pembrolizumabExtracranial disease progressionHigher adverse eventsPercentage of patientsPhase 2 studyPhase 2 trialSolid tumor malignanciesFraction of patientsDefinitive progressionUnacceptable toxicityAdverse eventsOverall survivalPatients 17Leptomeningeal carcinomatosisLeptomeningeal disseminationLung cancerDisease progressionOvarian cancerMetastatic cancerPembrolizumabBreast cancerGrade 3Patients
2019
Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L, Schneider BP, Shen F, Fuhrman K, Baltay M, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Overmoyer B, Partridge AH, Hudis CA, Krop IE, Burstein HJ, Winer EP. Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer. Journal Of Clinical Oncology 2019, 37: jco.19.00066. PMID: 30939096, PMCID: PMC7587424, DOI: 10.1200/jco.19.00066.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBreast NeoplasmsBreast Neoplasms, MaleChemotherapy, AdjuvantDisease-Free SurvivalFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseGenotypeHumansLymph NodesMaleMiddle AgedPaclitaxelPeripheral Nervous System DiseasesPoisson DistributionPolymorphism, Single NucleotideReceptor, ErbB-2RecurrenceRiskTrastuzumabTreatment OutcomeConceptsDisease-free survivalRecurrence-free intervalSmall HER2-positive tumorsAdjuvant paclitaxelHER2-positive tumorsLong-term outcomesTrastuzumab trialsBreast cancerOverall survivalSmall human epidermal growth factor receptor 2Breast cancer-specific survivalPaclitaxel-induced peripheral neuropathyExcellent long-term outcomesHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Human epidermal growth factor receptorPAM50 intrinsic subtypesCancer-specific survivalPhase II studyPrimary end pointGrowth factor receptor 2Positive breast cancerTreatment of patientsSeven-year followThe immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial
Barroso-Sousa R, Barry WT, Guo H, Dillon D, Tan YB, Fuhrman K, Osmani W, Getz A, Baltay M, Dang C, Yardley D, Moy B, Marcom PK, Mittendorf EA, Krop IE, Winer EP, Tolaney SM. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Annals Of Oncology 2019, 30: 575-581. PMID: 30753274, PMCID: PMC8033534, DOI: 10.1093/annonc/mdz047.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorBreastBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMastectomyMiddle AgedPaclitaxelReceptor, ErbB-2TrastuzumabTumor BurdenTumor MicroenvironmentConceptsHER2-positive breast cancerSmall HER2-positive breast cancersImmune gene signaturesBreast cancerImmune profileAPT trialPD-L1Immune markersImmune microenvironmentSmall HER2-positive tumorsStromal PD-L1 expressionNode-negative breast cancerCell signatureGene signatureHuman epidermal growth factor receptorStromal PD-L1PD-L1 expressionHistological grade 2Luminal B tumorsB cell signaturesBreast cancer trialsHER2-positive tumorsImmune cell signaturesBasal-like tumorsHistological grade 1
2018
Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer
Dickler MN, Saura C, Richards DA, Krop IE, Cervantes A, Bedard PL, Patel MR, Pusztai L, Oliveira M, Cardenas AK, Cui N, Wilson TR, Stout TJ, Wei MC, Hsu JY, Baselga J. Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer. Clinical Cancer Research 2018, 24: 4380-4387. PMID: 29793946, PMCID: PMC6139036, DOI: 10.1158/1078-0432.ccr-18-0613.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDisease-Free SurvivalDrug-Related Side Effects and Adverse ReactionsFemaleFulvestrantHumansImidazolesMiddle AgedMutationOxazepinesReceptor, ErbB-2Receptors, EstrogenConceptsAdverse eventsClinical activityBreast cancerMutation statusOpen-label phase II studyHR-positive breast cancerHigher objective response rateConfirmatory phase III trialNCI CTCAE v4.0Median treatment durationObjective response ratePhase II studySerious adverse eventsNew safety signalsPhase III trialsPositive breast cancerClin Cancer ResIntramuscular fulvestrantMeasurable diseaseRECIST v1.1II studyIII trialsPostmenopausal womenUnacceptable toxicityTumor response
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 discontinuation
2016
Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant
Spoerke JM, Gendreau S, Walter K, Qiu J, Wilson TR, Savage H, Aimi J, Derynck MK, Chen M, Chan IT, Amler LC, Hampton GM, Johnston S, Krop I, Schmid P, Lackner MR. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nature Communications 2016, 7: 11579. PMID: 27174596, PMCID: PMC4869259, DOI: 10.1038/ncomms11579.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreastBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDisease-Free SurvivalDNA Mutational AnalysisDNA, NeoplasmDrug Resistance, NeoplasmEstradiolEstrogen Receptor alphaEstrogen Receptor AntagonistsEstrogensFemaleFulvestrantHumansIndazolesMiddle AgedMutationProtein Kinase InhibitorsSulfonamidesConceptsMetastatic breast cancer patientsESR1 mutationsBreast cancer patientsCancer patientsPan-PI3K inhibitorPIK3CA-mutated tumorsProgression-free survivalMetastatic breast cancerWild-type patientsClinical trial samplesMutation allele frequencyInhibitor therapyFulvestrant treatmentBreast cancerClinical significanceClinical resistancePatientsBaseline samplesHotspot mutationsK inhibitorsTherapyLongitudinal analysisTrial samplesESR1Distinct clonesCardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer
Dang C, Guo H, Najita J, Yardley D, Marcom K, Albain K, Rugo H, Miller K, Ellis M, Shapira I, Wolff AC, Carey LA, Moy B, Groarke J, Moslehi J, Krop I, Burstein HJ, Hudis C, Winer EP, Tolaney SM. Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer. JAMA Oncology 2016, 2: 1-8. PMID: 26539793, PMCID: PMC5654518, DOI: 10.1001/jamaoncol.2015.3709.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalDrug Administration ScheduleFemaleHumansMiddle AgedNeoplasm StagingPaclitaxelReceptor, ErbB-2Risk AssessmentRisk FactorsStroke VolumeTime FactorsTrastuzumabTreatment OutcomeUnited StatesVentricular Dysfunction, LeftVentricular Function, LeftYoung AdultConceptsErbB2-positive breast cancerAsymptomatic LVEF declineCardiac toxic effectsLVEF declineBreast cancerPatients LVEFGrade 3Early-stage human epidermal growth factor receptor 2Asymptomatic left ventricular ejection fraction declineLeft ventricular ejection fraction declineVentricular ejection fraction declineHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Adjuvant weekly paclitaxelCardiac safety dataEjection fraction declineMedian patient ageVentricular systolic dysfunctionTrastuzumab-based treatmentWeeks of chemotherapyGrowth factor receptor 2Positive breast cancerLife-saving therapyFactor receptor 2Single-group study
2015
Phase 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 rateAdjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer
Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop IE, Burstein HJ, Winer EP. Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer. New England Journal Of Medicine 2015, 372: 134-141. PMID: 25564897, PMCID: PMC4313867, DOI: 10.1056/nejmoa1406281.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleFollow-Up StudiesHumansInfusions, IntravenousMastectomy, SegmentalMiddle AgedNeoplasm Recurrence, LocalPaclitaxelRadiotherapyReceptor, ErbB-2Survival RateTrastuzumabConceptsHER2-positive breast cancerBreast cancerAdjuvant paclitaxelEjection fractionInvasive diseaseStage I HER2-positive breast cancerHuman epidermal growth factor receptor type 2Epidermal growth factor receptor type 2Symptomatic congestive heart failureHER2-negative breast cancerLeft ventricular ejection fractionDistant metastatic breast cancerFactor receptor type 2Discontinuation of trastuzumabGrade 3 neuropathySingle standard treatmentPrimary end pointCongestive heart failureMetastatic breast cancerVentricular ejection fractionPositive breast cancerInvestigator-initiated studyReceptor type 2Disease-specific eventsMedian follow
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 eventsTrastuzumab 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 group
2013
A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive breast cancer
Tolaney SM, Najita J, Sperinde J, Huang W, Chen WY, Savoie J, Fornier M, Winer EP, Bunnell C, Krop IE. A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive breast cancer. Annals Of Oncology 2013, 24: 1841-1847. PMID: 23559151, PMCID: PMC3690910, DOI: 10.1093/annonc/mdt121.Peer-Reviewed Original ResearchConceptsMetastatic HER2-positive breast cancerHER2-positive breast cancerCombination of ixabepilonePhase II studyBreast cancerII studyMetastatic diseaseCohort 2Cohort 1Treatment-related toxic effectsClinical benefit rateSubsequent-line therapyTrastuzumab-containing regimensMetastatic breast cancerPrior chemotherapyLine therapyBenefit rateOverall RRDay 1PatientsTrastuzumabIxabepiloneCancerTumor biomarkersCohort
2012
Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer
Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K. Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. New England Journal Of Medicine 2012, 367: 1783-1791. PMID: 23020162, PMCID: PMC5125250, DOI: 10.1056/nejmoa1209124.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCapecitabineDeoxycytidineDisease-Free SurvivalFemaleFluorouracilHumansIntention to Treat AnalysisKaplan-Meier EstimateLapatinibMaytansineMiddle AgedNeoplasm MetastasisQuinazolinesReceptor, ErbB-2Survival RateTrastuzumabYoung AdultConceptsHER2-positive advanced breast cancerAdvanced breast cancerProgression-free survivalObjective response rateSecondary end pointsT-DM1Overall survivalBreast cancerEnd pointTrastuzumab emtansineInterim analysisResponse rateAdditional secondary end pointsMedian progression-free survivalHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Incidence of thrombocytopeniaMedian overall survivalPrimary end pointSerum aminotransferase levelsPalmar-plantar erythrodysesthesiaSecond interim analysisGrowth factor receptor 2Incidence of diarrheaFactor receptor 2A Phase II Study of Trastuzumab Emtansine in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab, Lapatinib, an Anthracycline, a Taxane, and Capecitabine
Krop IE, LoRusso P, Miller KD, Modi S, Yardley D, Rodriguez G, Guardino E, Lu M, Zheng M, Girish S, Amler L, Winer EP, Rugo HS. A Phase II Study of Trastuzumab Emtansine in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab, Lapatinib, an Anthracycline, a Taxane, and Capecitabine. Journal Of Clinical Oncology 2012, 30: 3234-3241. PMID: 22649126, DOI: 10.1200/jco.2011.40.5902.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAnthracyclinesAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsBridged-Ring CompoundsCapecitabineDeoxycytidineDisease-Free SurvivalFemaleFluorouracilHumansImmunotoxinsLapatinibMaleMaytansineMiddle AgedMolecular Targeted TherapyNeoplasm MetastasisQuinazolinesReceptor, ErbB-2TaxoidsTrastuzumabConceptsHER2-positive metastatic breast cancerHuman epidermal growth factor receptor 2Metastatic breast cancerProgression-free survivalOverall response rateMedian progression-free survivalPhase II studyT-DM1II studyTrastuzumab emtansineBreast cancerResponse rateSingle-arm phase II studyEpidermal growth factor receptor 2Human epidermal growth factor receptorClinical benefit rateHER2-directed therapiesMost adverse eventsGrowth factor receptor 2Single-agent activityHER2-positive tumorsMultiple chemotherapy agentsEffective new treatmentsFactor receptor 2Epidermal growth factor receptor
2011
Phase I/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy
Morrow PK, Wulf GM, Ensor J, Booser DJ, Moore JA, Flores PR, Xiong Y, Zhang S, Krop IE, Winer EP, Kindelberger DW, Coviello J, Sahin AA, Nuñez R, Hortobagyi GN, Yu D, Esteva FJ. Phase I/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy. Journal Of Clinical Oncology 2011, 29: 3126-3132. PMID: 21730275, PMCID: PMC3157979, DOI: 10.1200/jco.2010.32.2321.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDisease-Free SurvivalEverolimusFemaleHumansImmunohistochemistryKaplan-Meier EstimateMiddle AgedNeoplasm MetastasisPTEN PhosphohydrolaseReceptor, ErbB-2Salvage TherapySirolimusTOR Serine-Threonine KinasesTrastuzumabConceptsHER2-overexpressing metastatic breast cancerMetastatic breast cancerProgression-free survivalCombination of everolimusTrastuzumab-based therapyPTEN lossBreast cancerPhase I/II studyMedian progression-free survivalDana-Farber Cancer InstituteTexas MD Anderson Cancer CenterMD Anderson Cancer CenterBeth Israel Deaconess Medical CenterClinical benefit ratePersistent stable diseaseAnderson Cancer CenterDownstream mammalian targetDaily everolimusNonhematologic toxicityStable diseaseII studyOverall survivalPartial responseHER2 overexpressingClinical benefit