2023
Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01) ☆
Saura C, Modi S, Krop I, Park Y, Kim S, Tamura K, Iwata H, Tsurutani J, Sohn J, Mathias E, Liu Y, Cathcart J, Singh J, Yamashita T. Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01) ☆. Annals Of Oncology 2023, 35: 302-307. PMID: 38092229, PMCID: PMC11322859, DOI: 10.1016/j.annonc.2023.12.001.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerTreatment-emergent adverse eventsMetastatic breast cancerObjective response rateProgression-free survivalDuration of responseIndependent central reviewT-DXdAdverse eventsOverall survivalTrastuzumab deruxtecanCentral reviewBreast cancerDrug-related treatment-emergent adverse eventsInterstitial lung disease/pneumonitisResponse rateMedian progression-free survivalPositive metastatic breast cancerHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Sustained antitumor activityAntitumor activityMedian overall survivalPrimary end pointTrastuzumab 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 2
2018
369TiP PATINA: A randomized, open label, phase III trial to evaluate the efficacy and safety of palbociclib + Anti-HER2 therapy + endocrine therapy (ET) vs. anti-HER2 therapy + ET after induction treatment for hormone receptor positive (HR+)/HER2-positive metastatic breast cancer (MBC)
Loibl S, Metzger O, Mandrekar S, Mundhenke C, Seiler S, Valagussa P, DeMichele A, Lim E, Tripathy D, Winer E, Huang C, Carey L, Francis P, Miller K, Goetz M, Prat A, Loi S, Krop I, Gianni L, Ciruelos E. 369TiP PATINA: A randomized, open label, phase III trial to evaluate the efficacy and safety of palbociclib + Anti-HER2 therapy + endocrine therapy (ET) vs. anti-HER2 therapy + ET after induction treatment for hormone receptor positive (HR+)/HER2-positive metastatic breast cancer (MBC). Annals Of Oncology 2018, 29: viii121. DOI: 10.1093/annonc/mdy272.357.Peer-Reviewed Original Research
2015
Trastuzumab 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 2
2013
An Integrated Multiple-Analyte Pharmacokinetic Model to Characterize Trastuzumab Emtansine (T-DM1) Clearance Pathways and to Evaluate Reduced Pharmacokinetic Sampling in Patients with HER2-Positive Metastatic Breast Cancer
Lu D, Joshi A, Wang B, Olsen S, Yi JH, Krop IE, Burris HA, Girish S. An Integrated Multiple-Analyte Pharmacokinetic Model to Characterize Trastuzumab Emtansine (T-DM1) Clearance Pathways and to Evaluate Reduced Pharmacokinetic Sampling in Patients with HER2-Positive Metastatic Breast Cancer. Clinical Pharmacokinetics 2013, 52: 657-672. PMID: 23553425, DOI: 10.1007/s40262-013-0060-y.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerIntegrated population pharmacokinetic modelTotal trastuzumabPopulation pharmacokinetic modelT-DM1Pharmacokinetic dataPharmacokinetic profileBreast cancerClearance pathwaysPharmacokinetic samplingPharmacokinetic modelHER2-positive metastatic breast cancerPositive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Cytotoxic agent DM1Growth factor receptor 2T-DM1 treatmentEnd of infusionFactor receptor 2Serum concentration dataMonoclonal antibody trastuzumabTrastuzumab pharmacokineticsFaster clearance rateTaxane chemotherapy
2012
Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody–drug conjugate in development for the treatment of HER2-positive cancer
Girish S, Gupta M, Wang B, Lu D, Krop IE, Vogel CL, Burris III HA, LoRusso PM, Yi JH, Saad O, Tong B, Chu YW, Holden S, Joshi A. Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody–drug conjugate in development for the treatment of HER2-positive cancer. Cancer Chemotherapy And Pharmacology 2012, 69: 1229-1240. PMID: 22271209, PMCID: PMC3337408, DOI: 10.1007/s00280-011-1817-3.Peer-Reviewed Original ResearchConceptsSingle-agent T-DM1Anti-therapeutic antibodiesT-DM1 exposureTotal trastuzumabT-DM1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Standard noncompartmental approachT-DM1 pharmacokineticsGrowth factor receptor 2Key adverse eventsMetastatic breast cancerHER2-positive cancersStable thioether linkerConcentrations of transaminasesFactor receptor 2Enzyme-linked immunosorbent assayEnzyme-linked immunosorbentHER2 extracellular domainAntibody-drug conjugatesEvaluable patientsPrior therapyClinical responseAdverse events
2011
Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer
Olson EM, Lin NU, DiPiro PJ, Najita JS, Krop IE, Winer EP, Burstein HJ. Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer. Annals Of Oncology 2011, 23: 93-97. PMID: 21531783, PMCID: PMC3276325, DOI: 10.1093/annonc/mdr061.Peer-Reviewed Original ResearchConceptsAnti-HER2 therapyMetastatic breast cancerHER2-positive MBC patientsT-DM1MBC patientsBreast cancerHER2-positive metastatic breast cancerSingle-agent T-DM1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Blinded radiology reviewAnti-HER2 agentsGrowth factor receptor 2Kaplan-Meier estimatesFurther clinical benefitFactor receptor 2Protocol therapyMedian durationFurther therapyPartial responseRadiology reviewClinical benefitSubsequent linesMetastatic therapy