2024
A Pooled Analysis of Trastuzumab Deruxtecan in Patients With HER2-Positive Metastatic Breast Cancer With Brain Metastases
André F, Cortés J, Curigliano G, Modi S, Li W, Park Y, Chung W, Kim S, Yamashita T, Pedrini J, Im S, Tseng L, Harbeck N, Krop I, Nakatani S, Tecson K, Ashfaque S, Egorov A, Hurvitz S. A Pooled Analysis of Trastuzumab Deruxtecan in Patients With HER2-Positive Metastatic Breast Cancer With Brain Metastases. Annals Of Oncology 2024 PMID: 39241960, DOI: 10.1016/j.annonc.2024.08.2347.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerBlinded independent central reviewMetastatic breast cancerBrain metastasesT-DXdOverall survivalCNS-PFSTrastuzumab deruxtecanBreast cancerCentral nervous system progression-free survivalIntracranial responsePooled analysisIntracranial objective response rateSafety of trastuzumab deruxtecanSystemic progression-free survivalObjective response rateORR of patientsProgression-free survivalDuration of responseFood and Drug Administration criteriaIndependent central reviewUS Food and Drug Administration criteriaCompare treatmentsExploratory pooled analysisBM statusOutcomes with trastuzumab deruxtecan (T-DXd) by HER2 status and line of treatment in a large real-world database of patients with metastatic breast cancer.
Tarantino P, Lee D, Foldi J, Soulos P, Gross C, Grinda T, Winer E, Lin N, Krop I, Tolaney S, Lustberg M, Sammons S. Outcomes with trastuzumab deruxtecan (T-DXd) by HER2 status and line of treatment in a large real-world database of patients with metastatic breast cancer. Journal Of Clinical Oncology 2024, 42: 1077-1077. DOI: 10.1200/jco.2024.42.16_suppl.1077.Peer-Reviewed Original ResearchReal-world progression-free survivalLines of therapyMetastatic breast cancerMedian real-world progression-free survivalT-DXdHER2+Overall survivalHER2-lowHER2- patientsBreast cancerHER2- metastatic breast cancerTreat metastatic breast cancerProgression-free survivalKaplan-Meier methodLines of treatmentDatabase of patientsRetrospective observational studyClinical trial settingHER2 casesIHC 0Trastuzumab deruxtecanHR statusHER2 statusTriple-negativeMedian agePooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03.
Saura C, Cortés J, Modi S, Kim S, Hamilton E, Hurvitz S, Krop I, Curigliano G, Iwata H, Im S, Herbolsheimer P, Karnoub M, Gambhire D, Egorov A, Andre F. Pooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03. Journal Of Clinical Oncology 2024, 42: 1023-1023. DOI: 10.1200/jco.2024.42.16_suppl.1023.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsHER2+ metastatic breast cancerProgression-free survivalMetastatic breast cancerComplete responsePartial responseT-DXdOverall survivalPooled analysisInterstitial lung disease (ILD)/pneumonitisStable disease (SD)/progressive diseaseProlonged progression-free survivalDuration of responseIndependent central reviewNumerically lower ratesLonger treatment durationMetastatic settingRECIST v1.1Trastuzumab deruxtecanOS outcomesCentral reviewAdverse eventsBreast cancerTreatment durationDrug-related186P Exploratory pooled safety analysis of trastuzumab deruxtecan (T-DXd) in patients With HER2+ or HER2-low unresectable and/or metastatic breast cancer (mBC) in DESTINY-Breast trials
Park Y, Jacot W, Hurvitz S, Modi S, Yamashita T, Xu B, Tokunaga E, Wang X, Lee K, Iwata H, Krop I, André F, Harbeck N, Rugo H, Mathias E, Pasteiner W, Karnoub M, Ashfaque S, Cheng Y, Kim S. 186P Exploratory pooled safety analysis of trastuzumab deruxtecan (T-DXd) in patients With HER2+ or HER2-low unresectable and/or metastatic breast cancer (mBC) in DESTINY-Breast trials. ESMO Open 2024, 9: 103208. DOI: 10.1016/j.esmoop.2024.103208.Peer-Reviewed Original Research188P A health-related quality-of-life (HRQoL) analysis from DESTINY-Breast04: Trastuzumab deruxtecan (T-DXd) vs capecitabine (CAP) in patients (Pts) with hormone receptor-positive (HR+), HER2-low metastatic breast cancer (mBC)
Ueno N, Cottone F, Dunton K, Cardoso F, Yamashita T, Losada M, Niikura N, Zagouri F, Sohn J, Gombos A, Im S, Pierga J, Krop I, Hashimoto Y, Kim J, Gori S, Jacot W, Bauer R, Aguilar C, Modi S. 188P A health-related quality-of-life (HRQoL) analysis from DESTINY-Breast04: Trastuzumab deruxtecan (T-DXd) vs capecitabine (CAP) in patients (Pts) with hormone receptor-positive (HR+), HER2-low metastatic breast cancer (mBC). ESMO Open 2024, 9: 103210. DOI: 10.1016/j.esmoop.2024.103210.Peer-Reviewed Original Research182MO Trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2+ metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1): Updated overall survival (OS) results of the randomized phase III DESTINY-breast (DB-)02 study
Kim S, André F, Takano T, Fehm T, Park Y, Lee J, Borges G, Kaplan M, Kaczmarek E, Guarneri V, Yonemori K, Pluard T, Prat A, Paterson F, Oakman C, Nakatani S, Ashfaque S, Lu W, Egorov A, Krop I. 182MO Trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with HER2+ metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1): Updated overall survival (OS) results of the randomized phase III DESTINY-breast (DB-)02 study. ESMO Open 2024, 9: 103204. DOI: 10.1016/j.esmoop.2024.103204.Peer-Reviewed Original Research
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 pointAn age-specific pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03.
Krop I, Wildiers H, Hurvitz S, Cortes J, Im S, Iwata H, Andre F, Saura C, Modi S, Kim S, Egorov A, Mathias E, Cathcart J, Cagnazzo A, Cheng Y, Park Y. An age-specific pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03. Journal Of Clinical Oncology 2023, 41: 1006-1006. DOI: 10.1200/jco.2023.41.16_suppl.1006.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsMetastatic breast cancerT-DXdGrade treatment-emergent adverse eventsHER2-positive metastatic breast cancerInterstitial lung disease/pneumonitisFavorable benefit-risk profileAge-specific efficacyGrade 5 eventsPooled safety analysisBenefit-risk profileYears of ageKey efficacy dataOlder ptsSerious AEsAdverse eventsTrastuzumab deruxtecanAdditional efficacyPooled analysisT-DM1Trastuzumab emtansineEfficacy dataBreast cancerSafety dataSafety outcomes
2022
Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis
Jerusalem G, Park YH, Yamashita T, Hurvitz S, Modi S, Andre F, Krop I, Farré X, You B, Saura C, Kim S, Osborne C, Murthy R, Gianni L, Takano T, Liu Y, Cathcart J, Lee C, Perrin C. Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis. Cancer Discovery 2022, 12: 2754-2762. PMID: 36255231, PMCID: PMC9716244, DOI: 10.1158/2159-8290.cd-22-0837.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalMetastatic breast cancerHER2-positive metastatic breast cancerBrain metastasesT-DXdTrastuzumab deruxtecanBreast cancerHER2-positive metastatic breast cancer patientsMetastatic breast cancer patientsDurable clinical activityObjective response rateProgression-free survivalBreast cancer patientsLimited treatment optionsPopulation warrants further investigationBest percentage changeWarrants further investigationIntracranial progressionStable diseasePartial responseComplete responseDurable efficacySafety profileTherapeutic optionsTreatment options
2021
Trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer with brain metastases: A subgroup analysis of the DESTINY-Breast01 trial.
Jerusalem G, Park Y, Yamashita T, Hurvitz S, Modi S, Andre F, Krop I, Gonzalez X, Hall P, You B, Saura C, Kim S, Osborne C, Sagara Y, Tokunaga E, Liu Y, Cathcart J, Lee C, Perrin C. Trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer with brain metastases: A subgroup analysis of the DESTINY-Breast01 trial. Journal Of Clinical Oncology 2021, 39: 526-526. DOI: 10.1200/jco.2021.39.15_suppl.526.Peer-Reviewed Original ResearchMetastatic breast cancerMedian progression-free survivalObjective response rateBrain metastasesT-DXdSubgroup analysisClinical activityBreast cancerResponse rateTopoisomerase I inhibitor payloadBaseline brain metastasesDurable clinical activityNon-target lesionsSubgroups of ptsPhase 2 trialProgression-free survivalTreatment of adultsIndependent central reviewSystemic disease controlStrong clinical activityAnti-HER2 antibodyAdult ptsBM diameterPrior chemotherapyMedian durationHER2CLIMB-04: Phase 2 open label trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ unresectable locally advanced or metastatic breast cancer with and without brain metastases (trial in progress).
Krop I, Ramos J, Zhang C, Hamilton E. HER2CLIMB-04: Phase 2 open label trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ unresectable locally advanced or metastatic breast cancer with and without brain metastases (trial in progress). Journal Of Clinical Oncology 2021, 39: tps1097-tps1097. DOI: 10.1200/jco.2021.39.15_suppl.tps1097.Peer-Reviewed Original ResearchHuman epidermal growth factor receptor 2Metastatic breast cancerProgression-free survivalDisease control rateDuration of responseBrain metastasesOverall survivalT-DXdEpidermal growth factor receptorRECIST v1.1Metastatic settingTrastuzumab deruxtecanBreast cancerOpen-label phase 2 trialPhase 2 open-label trialSmall molecule tyrosine kinase inhibitorsTopoisomerase I inhibitor payloadTreatment of HER2Epidermal growth factor receptor 2Molecule tyrosine kinase inhibitorsHuman epidermal growth factor receptorActive brain metastasesCombination of tucatinibSolid Tumors v1.1Objective response rate
2020
Trastuzumab deruxtecan for HER2-positive metastatic breast cancer: DESTINY-Breast01 subgroup analysis.
Modi S, Andre F, Krop I, Saura C, Yamashita T, Kim S, Tamura K, Chen S, Suto F, Kuwahara Y, Lee C, Park Y. Trastuzumab deruxtecan for HER2-positive metastatic breast cancer: DESTINY-Breast01 subgroup analysis. Journal Of Clinical Oncology 2020, 38: 1036-1036. DOI: 10.1200/jco.2020.38.15_suppl.1036.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerMedian progression-free survivalObjective response rateMetastatic breast cancerT-DXdTrastuzumab deruxtecanClinical subgroupsBreast cancerHormone receptor positive statusImproved objective response rateCox proportional hazards modelClinical predictor variablesHER2 IHC 3Prior treatment regimensPhase II trialProgression-free survivalProgesterone receptor statusBiomarkers of efficacyEnd of treatmentCycles of treatmentProportional hazards modelAnti-HER2 antibodyLogistic regression modelsERBB2 copy numberTopoisomerase I inhibitorTargeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors
Tsurutani J, Iwata H, Krop I, Jänne PA, Doi T, Takahashi S, Park H, Redfern C, Tamura K, Wise-Draper TM, Saito K, Sugihara M, Singh J, Jikoh T, Gallant G, Li BT. Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors. Cancer Discovery 2020, 10: 688-701. PMID: 32213540, PMCID: PMC8292921, DOI: 10.1158/2159-8290.cd-19-1014.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerMutant non-small cell lung cancerTreatment-emergent adverse eventsMutant solid tumorsObjective response rateProgression-free survivalMedian progression-free survivalT-DXdSolid tumorsTrastuzumab deruxtecanDrug-related treatment-emergent adverse eventsCommon treatment-emergent adverse eventsConfirmed objective response rateSafety/tolerabilityAdvanced solid tumorsBiliary tract cancerPhase I trialHER2-positive breastInterstitial lung diseaseCell lung cancerSalivary gland cancerHeterogeneous patient populationUnmet medical needConfirmed responsesDose expansionAntitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study
Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, Moreno-Aspitia A, Doi T, Sagara Y, Redfern C, Krop IE, Lee C, Fujisaki Y, Sugihara M, Zhang L, Shahidi J, Takahashi S. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study. Journal Of Clinical Oncology 2020, 38: 1887-1896. PMID: 32058843, PMCID: PMC7280051, DOI: 10.1200/jco.19.02318.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseHER2-low breast cancerT-DXdBreast cancerTrastuzumab deruxtecanAntitumor activityConfirmed objective response rateTopoisomerase I inhibitor payloadTreatment-emergent adverse eventsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Breast cancer refractoryIndependent adjudication committeeObjective response ratePhase Ib studyAdvanced breast cancerGrowth factor receptor 2Preliminary antitumor activityIndependent central reviewWithdrawal of consentFactor receptor 2Cancer refractoryEligible patientsMetastatic HER2Unacceptable toxicity