2024
Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial
Fehm T, Cottone F, Dunton K, André F, Krop I, Park Y, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego M, Yerushalmi R, Duhoux F, Takano T, Lu W, Egorov A, Kim S. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. The Lancet Oncology 2024, 25: 614-625. PMID: 38697155, DOI: 10.1016/s1470-2045(24)00128-1.Peer-Reviewed Original ResearchConceptsTreatment of physician's choiceMetastatic breast cancerTreatment of physician's choice groupPatient-reported outcomesPhysician's choice groupTrastuzumab deruxtecan groupTrastuzumab deruxtecanPhase 3 trialHER2-positiveBreast cancerGlobal health statusPhysician's choiceEORTC QLQ-C30 global health statusPatient-reported outcome variablesOpen-labelQLQ-C30 global health statusTrastuzumab emtansineDefinitive deteriorationMedian time to definitive deteriorationHER2-positive metastatic breast cancerEastern Cooperative Oncology Group performance statusTreatment durationBlinded independent central reviewQuality of lifeProgression-free survival
2023
Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial
André F, Hee Park Y, Kim S, Takano T, Im S, Borges G, Lima J, Aksoy S, Gavila Gregori J, De Laurentiis M, Bianchini G, Roylance R, Miyoshi Y, Armstrong A, Sinha R, Ruiz Borrego M, Lim E, Ettl J, Yerushalmi R, Zagouri F, Duhoux F, Fehm T, Gambhire D, Cathcart J, Wu C, Chu C, Egorov A, Krop I. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. The Lancet 2023, 401: 1773-1785. PMID: 37086745, DOI: 10.1016/s0140-6736(23)00725-0.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerPhysician's choice groupTreatment-emergent adverse eventsBlinded independent central reviewPhase 3 trialProgression-free survivalTrastuzumab deruxtecanIndependent central reviewBreast cancerPhysician's choiceAdverse eventsCentral reviewTrastuzumab emtansineEastern Cooperative Oncology Group performance statusCommon treatment-emergent adverse eventsHigher treatment-emergent adverse eventsMedian progression-free survivalPositive metastatic breast cancerFavorable benefit-risk profilePalmar-plantar erythrodysaesthesiaInterstitial lung diseaseBenefit-risk profileAntibody-drug conjugatesChoice groupTucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases
Lin N, Murthy R, Abramson V, Anders C, Bachelot T, Bedard P, Borges V, Cameron D, Carey L, Chien A, Curigliano G, DiGiovanna M, Gelmon K, Hortobagyi G, Hurvitz S, Krop I, Loi S, Loibl S, Mueller V, Oliveira M, Paplomata E, Pegram M, Slamon D, Zelnak A, Ramos J, Feng W, Winer E. Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases. JAMA Oncology 2023, 9: 197-205. PMID: 36454580, PMCID: PMC9716438, DOI: 10.1001/jamaoncol.2022.5610.Peer-Reviewed Original ResearchConceptsErbB2-positive metastatic breast cancerMetastatic breast cancerPlacebo-combination groupPositive metastatic breast cancerNew brain lesionsBrain metastasesOverall survivalSubgroup analysisBrain lesionsBreast cancerIntracranial progression-free survivalPlacebo-controlled clinical trialIntracranial objective response rateStable brain metastasesMedian overall survivalObjective response rateProgression-free survivalExploratory subgroup analysisGreater clinical benefitCNS-PFSHER2CLIMB trialIntracranial outcomesFirst progressionMedian ageClinical benefit
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 subgroups
2019
Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer
Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. New England Journal Of Medicine 2019, 382: 597-609. PMID: 31825569, DOI: 10.1056/nejmoa1914609.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsBreast NeoplasmsCapecitabineConsolidation ChemotherapyDiarrheaDouble-Blind MethodFemaleHumansKaplan-Meier EstimateMiddle AgedOxazolesProgression-Free SurvivalProtein-Tyrosine KinasesPyridinesQuinazolinesReceptor, ErbB-2TrastuzumabConceptsHER2-positive metastatic breast cancerProgression-free survivalPlacebo-combination groupMetastatic breast cancerElevated aminotransferase levelsBrain metastasesBreast cancerOverall survivalAminotransferase levelsMedian progression-free survivalPalmar-plantar erythrodysesthesia syndromeBetter progression-free survivalPositive metastatic breast cancerHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Common adverse eventsMedian overall survivalObjective response ratePrimary end pointSecondary end pointsGrowth factor receptor 2Overall survival outcomesRisk of diarrheaFactor receptor 2TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
Freedman RA, Gelman RS, Anders CK, Melisko ME, Parsons HA, Cropp AM, Silvestri K, Cotter CM, Componeschi KP, Marte JM, Connolly RM, Moy B, Van Poznak CH, Blackwell KL, Puhalla SL, Jankowitz RC, Smith KL, Ibrahim N, Moynihan TJ, O’Sullivan C, Nangia J, Niravath P, Tung N, Pohlmann PR, Burns R, Rimawi MF, Krop IE, Wolff AC, Winer EP, Lin NU, . TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases. Journal Of Clinical Oncology 2019, 37: jco.18.01511. PMID: 30860945, PMCID: PMC6494354, DOI: 10.1200/jco.18.01511.Peer-Reviewed Original ResearchConceptsCNS objective response rateObjective response rateHER2-positive breast cancer brain metastasesBreast cancer brain metastasesCancer brain metastasesBrain metastasesBreast cancerCommon grade 3 toxicitiesHER2-positive brain metastasesMedian progression-free survivalHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Human epidermal growth factor receptorEfficacy of HER2Non-CNS progressionGrade 3 toxicityPrimary end pointPhase II trialProgression-free survivalGrowth factor receptor 2Positive breast cancerProgressive neurologic signsEvidence-based treatmentsFactor receptor 2Epidermal growth factor receptor
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
Relationship between tumor biomarkers and efficacy in TH3RESA, a phase III study of trastuzumab emtansine (T‐DM1) vs. treatment of physician's choice in previously treated HER2‐positive advanced breast cancer
Kim S, Wildiers H, Krop IE, Smitt M, Yu R, de Haas S, Gonzalez‐Martin A. Relationship between tumor biomarkers and efficacy in TH3RESA, a phase III study of trastuzumab emtansine (T‐DM1) vs. treatment of physician's choice in previously treated HER2‐positive advanced breast cancer. International Journal Of Cancer 2016, 139: 2336-2342. PMID: 27428671, DOI: 10.1002/ijc.30276.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCapecitabineClass I Phosphatidylinositol 3-KinasesFemaleHumansKaplan-Meier EstimateLapatinibMaytansinePhosphatidylinositol 3-KinasesQuinazolinesReceptor, ErbB-2Trastuzumab
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 eventsA phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer
Tolaney SM, Jeong J, Guo H, Brock J, Morganstern D, Come SE, Golshan M, Bellon J, Winer EP, Krop IE. A phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer. Cancer Medicine 2014, 3: 293-299. PMID: 24464780, PMCID: PMC3987079, DOI: 10.1002/cam4.164.Peer-Reviewed Original ResearchConceptsHormone receptor-positive breast cancerReceptor-positive breast cancerPathological complete responsePositive breast cancerBreast cancerPreoperative capecitabineClinical responseHER2-negative operable breast cancerDihydropyrimidine dehydrogenaseOnly grade 3 toxicityOverall clinical response rateThymidine phosphorylaseGrade 3 responsePartial clinical responsePathological response assessmentsPreoperative chemotherapy regimensClinical response rateComplete clinical responseGrade 3 toxicityOperable breast cancerPhase II studyPalmar-plantar erythrodysesthesiaMetastatic breast cancerTime of surgeryMiller-Payne
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
2008
Ten years of HER2-directed therapy: still questions after all these years
Krop IE, Winer EP. Ten years of HER2-directed therapy: still questions after all these years. Breast Cancer Research And Treatment 2008, 113: 207-209. PMID: 18463974, DOI: 10.1007/s10549-008-0041-2.Peer-Reviewed Original ResearchAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCapecitabineClinical Trials, Phase III as TopicDeoxycytidineDisease-Free SurvivalDrug Delivery SystemsDrug Resistance, NeoplasmErbB ReceptorsFemaleFluorouracilForecastingHumansLapatinibNeoplasm ProteinsProtein Kinase InhibitorsQuinazolinesRandomized Controlled Trials as TopicReceptor, ErbB-2Trastuzumab