2024
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.
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-related
2022
Clinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) after prior treatment (tx) with FUL in patients (pts) with advanced breast cancer (ABC): A real-world (RW) analysis.
O'Shaughnessy J, Woeckel A, Pistilli B, Hegg R, Vahdat L, Vuina D, ZVK P, Smith T, Kim J, Krop I. Clinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) after prior treatment (tx) with FUL in patients (pts) with advanced breast cancer (ABC): A real-world (RW) analysis. Journal Of Clinical Oncology 2022, 40: 1055-1055. DOI: 10.1200/jco.2022.40.16_suppl.1055.Peer-Reviewed Original ResearchAdvanced breast cancerEndocrine-based therapyPIK3CA mutationsMetastatic settingClinical outcomesCyclin-dependent kinase 4/6 inhibitorsDe-identified electronic health record dataHuman epidermal growth factor receptorImmediate prior therapyLines of therapyProgression-free survivalProgression/deathElectronic health record dataDate of deathHealth record dataEpidermal growth factor receptorReal-world analysisGrowth factor receptorNCCN guidelinesPrior chemotherapyPrior therapyMedian durationMedian timeSubsequent therapyClinical benefit
2021
Pharmacokinetic (PK) analyses in CSF and plasma from TBCRC049, an ongoing trial to assess the safety and efficacy of the combination of tucatinib, trastuzumab and capecitabine for the treatment of leptomeningeal metastasis (LM) in HER2 positive breast cancer.
Stringer-Reasor E, O'Brien B, Topletz-Erickson A, White J, Lobbous M, Riley K, Childress J, LaMaster K, Melisko M, Morikawa A, De Groot J, Krop I, Valero V, Rimawi M, Wolff A, Tripathy D, Lin N, Murthy R. Pharmacokinetic (PK) analyses in CSF and plasma from TBCRC049, an ongoing trial to assess the safety and efficacy of the combination of tucatinib, trastuzumab and capecitabine for the treatment of leptomeningeal metastasis (LM) in HER2 positive breast cancer. Journal Of Clinical Oncology 2021, 39: 1044-1044. DOI: 10.1200/jco.2021.39.15_suppl.1044.Peer-Reviewed Original ResearchLeptomeningeal metastasesBrain metastasesBreast cancerPharmacokinetic analysisPhase 2 single-arm studyHER2-positive breast cancerCombination of tucatinibNew brain metastasesSingle-arm studyPositive breast cancerTyrosine kinase inhibitorsHigh interindividual variabilityMetastatic HER2Accrual goalEligible patientsMetastatic settingPrimary endpointOverall survivalOmmaya reservoirOngoing trialsPlasma concentrationsCapecitabinePatientsDay 1PK samplesHER2CLIMB-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 rateUpdated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB).
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, Zhang C, Winer E. Updated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB). Journal Of Clinical Oncology 2021, 39: 1043-1043. DOI: 10.1200/jco.2021.39.15_suppl.1043.Peer-Reviewed Original ResearchMetastatic breast cancerBrain metastasesOverall survivalTyrosine kinase inhibitorsBreast cancerPlacebo armAnalysis of OSOral tyrosine kinase inhibitorECOG performance statusPlacebo-controlled trialTotal study populationKaplan-Meier timeHER2CLIMB trialMeaningful prolongationMetastatic HER2Study medicationTolerability assessmentsMetastatic settingAdverse eventsDose modificationHazard ratioLast patientPerformance statusDisease progressionStudy population
2018
Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer
Kuang Y, Siddiqui B, Hu J, Pun M, Cornwell M, Buchwalter G, Hughes ME, Wagle N, Kirschmeier P, Jänne PA, Paweletz CP, Lin NU, Krop IE, Barry WT, Winer EP, Brown M, Jeselsohn R. Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer. Npj Breast Cancer 2018, 4: 22. PMID: 30083595, PMCID: PMC6072793, DOI: 10.1038/s41523-018-0075-5.Peer-Reviewed Original ResearchMetastatic breast cancerESR1 mutationsBreast cancerMetastatic settingClinicopathological featuresPIK3CA mutationsAromatase inhibitorsER-positive metastatic breast cancerDetailed clinical dataSpecific systemic treatmentMetastatic treatmentDistant recurrenceMetastatic diseaseSystemic treatmentPrimary diseaseEndocrine resistanceCDK4/6 inhibitorsPathological featuresFulvestrant treatmentClinical dataPrior treatmentSignificant associationPatientsCancerPrevalenceAssociation of Cell-Free DNA Tumor Fraction and Somatic Copy Number Alterations With Survival in Metastatic Triple-Negative Breast Cancer
Stover DG, Parsons HA, Ha G, Freeman SS, Barry WT, Guo H, Choudhury AD, Gydush G, Reed SC, Rhoades J, Rotem D, Hughes ME, Dillon DA, Partridge AH, Wagle N, Krop IE, Getz G, Golub TR, Love JC, Winer EP, Tolaney SM, Lin NU, Adalsteinsson VA. Association of Cell-Free DNA Tumor Fraction and Somatic Copy Number Alterations With Survival in Metastatic Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2018, 36: jco.2017.76.003. PMID: 29298117, PMCID: PMC5815405, DOI: 10.1200/jco.2017.76.0033.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerPrimary triple-negative breast cancerTumor fractionSomatic copy number alterationsCell-free DNABreast cancerSingle tertiary care institutionCopy number alterationsRetrospective cohort studySpecific somatic copy number alterationsTertiary care institutionNovel therapeutic approachesNumber alterationsCfDNA tumor fractionMetastatic survivalPrior chemotherapyTNBC cohortMetastatic settingCohort studyOverall survivalCancer Genome AtlasClinicopathologic factorsWorse survivalPrimary tumor
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 rate
2013
Beyond Trastuzumab and Lapatinib: New Options for HER2-Positive Breast Cancer
Zardavas D, Cameron D, Krop I, Piccart M. Beyond Trastuzumab and Lapatinib: New Options for HER2-Positive Breast Cancer. American Society Of Clinical Oncology Educational Book 2013, e2-e11. DOI: 10.14694/edbook_am.2013.33.e2.Peer-Reviewed Original ResearchHER2-positive breast cancerDual HER2 blockadeAntibody-drug conjugatesHER2 blockadeMetastatic settingBreast cancerAdjuvant settingTrastuzumab-DM1Clinical trialsSmall molecule inhibitorsClinical practiceMonoclonal antibodiesAnti-HER2 resistanceAnti-HER2 agentsLarge randomized trialsEfficacy of trastuzumabSubset of patientsAdvanced clinical testingHER2-targeted agentsNew treatment optionsAggressive biologic behaviorDrug conjugatesMajor clinical issueImproved treatment outcomesMolecule inhibitorsBeyond trastuzumab and lapatinib: new options for HER2-positive breast cancer .
Zardavas D, Cameron D, Krop I, Piccart M. Beyond trastuzumab and lapatinib: new options for HER2-positive breast cancer . American Society Of Clinical Oncology Educational Book 2013, 33: e2-e11. PMID: 23714441, DOI: 10.1200/edbook_am.2013.33.e2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsChemotherapy, AdjuvantDrug Resistance, NeoplasmFemaleHumansLapatinibMolecular Targeted TherapyNeoadjuvant TherapyProtein Kinase InhibitorsQuinazolinesReceptor, ErbB-2Signal TransductionTrastuzumabTreatment OutcomeConceptsHER2-positive breast cancerDual HER2 blockadeAntibody-drug conjugatesHER2 blockadeBreast cancerMetastatic settingClinical trialsAnti-HER2 resistanceAnti-HER2 agentsLarge randomized trialsHER2-targeted agentsNew treatment optionsAggressive biologic behaviorMajor clinical issueImproved treatment outcomesNew therapeutic avenuesDevelopment of agentsAdjuvant settingNeoadjuvant settingAdvanced diseaseTrastuzumab-DM1Randomized trialsTreatment optionsBiologic rationaleHER2 inhibition
2009
Quantitative assessment of HER2 status and correlation with efficacy for patients (pts) with metastatic breast cancer (MBC) in a phase II study of trastuzumab-DM1 (T-DM1)
Krop I, Burris H, Rugo H, O'Shaughnessy J, Vogel C, Amler L, Strauss A, Wong E, Klencke B, Pippen J. Quantitative assessment of HER2 status and correlation with efficacy for patients (pts) with metastatic breast cancer (MBC) in a phase II study of trastuzumab-DM1 (T-DM1). Journal Of Clinical Oncology 2009, 27: 1003-1003. DOI: 10.1200/jco.2009.27.15_suppl.1003.Peer-Reviewed Original ResearchMetastatic breast cancerEnzyme-linked immunosorbent assayPhase II studyPartial responseTrastuzumab-DM1II studyQRT-PCRGood responseSingle-arm studyT-DM1 therapyCentral laboratory testingAdditional diagnostic markerReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionAnti-microtubule agentsMedian 4.4Metastatic settingCorrelation of responseHER2 statusPolymerase chain reactionBreast cancerECD levelsMedian levelsResponse ratePT serum