2020
A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer
Barroso-Sousa R, Krop IE, Trippa L, Tan-Wasielewski Z, Li T, Osmani W, Andrews C, Dillon D, Richardson ET, Pastorello RG, Winer EP, Mittendorf EA, Bellon JR, Schoenfeld JD, Tolaney SM. A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer. Clinical Breast Cancer 2020, 20: 238-245. PMID: 32113750, DOI: 10.1016/j.clbc.2020.01.012.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBiomarkers, TumorBreastBreast NeoplasmsCarcinoma, Ductal, BreastChemoradiotherapyDrug Administration ScheduleFemaleHumansInfusions, IntravenousMiddle AgedPalliative CareProgrammed Cell Death 1 ReceptorProgression-Free SurvivalReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneResponse Evaluation Criteria in Solid TumorsConceptsMetastatic breast cancerHormone receptor-positive metastatic breast cancerProgression-free survivalRadiation therapyObjective responseOverall survivalBreast cancerResponse rateMedian progression-free survivalCause adverse eventsGrade 3 eventsMedian prior linesMedian overall survivalObjective response ratePalliative radiation therapyPhase II studyTumor-infiltrating lymphocytesLymph node lesionsOverall response rateEpidermal growth factor receptorEligible patientsExploratory endpointsGrowth factor receptorPalliative radiotherapyPrimary endpoint
2019
Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022
Freedman RA, Gelman RS, Agar NYR, Santagata S, Randall EC, Lopez B, Connolly RM, Dunn IF, Van Poznak CH, Anders CK, Melisko ME, Silvestri K, Cotter CM, Componeschi KP, Marte JM, Moy B, Blackwell KL, Puhalla SL, Ibrahim N, Moynihan TJ, Nangia J, Tung N, Burns R, Rimawi MF, Krop IE, Wolff AC, Winer EP, Lin NU, Consortium T. Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022. Clinical Breast Cancer 2019, 20: 145-151.e2. PMID: 31558424, PMCID: PMC7035200, DOI: 10.1016/j.clbc.2019.07.011.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAntineoplastic Combined Chemotherapy ProtocolsBrainBrain NeoplasmsBreastBreast NeoplasmsChemotherapy, AdjuvantCraniotomyDrug Administration ScheduleFemaleHumansMiddle AgedNeoadjuvant TherapyPilot ProjectsQuinolinesReceptor, ErbB-2Tissue DistributionTreatment OutcomeConceptsCentral nervous system penetrationCerebrospinal fluidBrain metastasesStudy treatmentDisease progressionHER2-positive breast cancer brain metastasesHER2-positive metastatic breast cancerHER2-positive brain metastasesBreast cancer brain metastasesGrade 3 diarrheaCancer brain metastasesMetastatic breast cancerCentral nervous systemResected tumor tissueBlood-based analysesNeratinib monotherapyPostoperative cyclesParenchymal tumorsStudy protocolBreast cancerTumor histopathologyPatientsNervous systemSmall cohortSurgical tissuesFirst‐in‐human, phase I study of PF‐06647263, an anti‐EFNA4 calicheamicin antibody–drug conjugate, in patients with advanced solid tumors
Garrido‐Laguna I, Krop I, Burris HA, Hamilton E, Braiteh F, Weise AM, Abu‐Khalaf M, Werner TL, Pirie‐Shepherd S, Zopf CJ, Lakshminarayanan M, Holland JS, Baffa R, Hong DS. First‐in‐human, phase I study of PF‐06647263, an anti‐EFNA4 calicheamicin antibody–drug conjugate, in patients with advanced solid tumors. International Journal Of Cancer 2019, 145: 1798-1808. PMID: 30680712, PMCID: PMC6875752, DOI: 10.1002/ijc.32154.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerAdvanced solid tumorsTumor responseSolid tumorsMetastatic triple-negative breast cancerPhase IPhase 2 doseAntitumor activityHuman xenograft tumor modelsAvailable standard therapiesDose-related mannerLimited antitumor activityXenograft tumor modelCommon AEsStable diseaseManageable safetyPartial responsePotent antitumor activityStandard therapyToxicity probability interval methodOvarian cancerBreast cancerPatientsRP2DTumor model
2018
Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study
Munster P, Krop IE, LoRusso P, Ma C, Siegel BA, Shields AF, Molnár I, Wickham TJ, Reynolds J, Campbell K, Hendriks BS, Adiwijaya BS, Geretti E, Moyo V, Miller KD. Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study. British Journal Of Cancer 2018, 119: 1086-1093. PMID: 30361524, PMCID: PMC6219487, DOI: 10.1038/s41416-018-0235-2.Peer-Reviewed Original ResearchConceptsOverall response rateAdverse eventsMM-302Breast cancerAdvanced HER2-positive breast cancerPhase 1 dose-escalation studyPhase 1 dose-escalation trialGrade 3/4 adverse eventsHER2-positive breast cancerAnthracycline-naïve patientsResultsSixty-nine patientsCommon adverse eventsDose-escalation studyDose-escalation trialPalmar-plantar erythrodysesthesiaMetastatic breast cancerFebrile neutropeniaMucosal inflammationPromising efficacyResponse rateTrastuzumabQ3wPatientsMonotherapyNeutropeniaTucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial
Borges VF, Ferrario C, Aucoin N, Falkson C, Khan Q, Krop I, Welch S, Conlin A, Chaves J, Bedard PL, Chamberlain M, Gray T, Vo A, Hamilton E. Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial. JAMA Oncology 2018, 4: 1214-1220. PMID: 29955792, PMCID: PMC6143009, DOI: 10.1001/jamaoncol.2018.1812.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAntineoplastic Combined Chemotherapy ProtocolsArea Under CurveBreast NeoplasmsDiarrheaDrug Administration ScheduleFatigueFemaleHumansKaplan-Meier EstimateMaytansineMiddle AgedNauseaNeoplasm MetastasisProtein Kinase InhibitorsReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsTrastuzumabConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdo-trastuzumab emtansineT-DM1Breast cancerTyrosine kinase inhibitorsBrain metastasesAdverse eventsClinical trialsToxic reactionsDose-limiting toxic reactionHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Phase 1b clinical trialGrowth factor receptor 2ERBB2/HER2-positive breast cancerPreliminary antitumor activityTreatment of patientsSpecific tyrosine kinase inhibitorYears of ageDrug-drug interactionsFactor receptor 2Hepatic transaminitisHER2 therapy
2016
Cardiac 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
Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo)Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2–Positive Early-Stage Breast Cancer
Krop IE, Suter TM, Dang CT, Dirix L, Romieu G, Zamagni C, Citron ML, Campone M, Xu N, Smitt M, Gianni L. Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo)Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2–Positive Early-Stage Breast Cancer. Journal Of Clinical Oncology 2015, 33: 1136-1142. PMID: 25713436, PMCID: PMC5657012, DOI: 10.1200/jco.2014.58.7782.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnthracyclinesAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCombined Modality TherapyCyclophosphamideDoxorubicinDrug Administration ScheduleEpirubicinFeasibility StudiesFluorouracilHeadacheHeart FailureHumansMaytansineMiddle AgedNauseaNeoplasm StagingReceptor, ErbB-2TrastuzumabTreatment OutcomeYoung AdultConceptsEarly-stage breast cancerHER2-positive early-stage breast cancerHuman epidermal growth factor receptorT-DM1Breast cancerEpidermal growth factor receptorGrowth factor receptorCardiac eventsCardiac safetyTrastuzumab emtansineSymptomatic congestive heart failureAsymptomatic LVEF declineCytotoxic agent DM1Planned radiation doseAnthracycline-based chemotherapyCoprimary end pointsPhase III trialsCongestive heart failureFactor receptorMetastatic breast cancerVentricular ejection fractionT-DM1 treatmentStage breast cancerLVEF declineAdverse eventsSU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer
Gonzalez-Angulo AM, Krop I, Akcakanat A, Chen H, Liu S, Li Y, Culotta KS, Tarco E, Piha-Paul S, Moulder-Thompson S, Velez-Bravo V, Sahin AA, Doyle LA, Do KA, Winer EP, Mills GB, Kurzrock R, Meric-Bernstam F. SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer. Journal Of The National Cancer Institute 2015, 107: dju493. PMID: 25688104, PMCID: PMC4342675, DOI: 10.1093/jnci/dju493.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDrug Administration ScheduleDrug EruptionsFatigueFemaleHeterocyclic Compounds, 3-RingHumansHyperglycemiaMaleMaximum Tolerated DoseMiddle AgedNeoplasmsNeutropeniaPaclitaxelSeverity of Illness IndexTreatment OutcomeConceptsDose escalationDay 1Day 2Higher adverse eventsPhase Ib studyWeeks of therapyAdvanced solid tumorsCTCAE grade 3Metastatic breast cancerPrevious phase IPreliminary antitumor activityDose expansionStable diseaseObjective responseUnacceptable toxicityAdverse eventsMedian ageWeekly dosesClinical benefitPharmacodynamic markersSystemic exposureExcessive toxicityTumor responseGrade 3Median number
2014
Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Giordano SH, Temin S, Kirshner JJ, Chandarlapaty S, Crews JR, Davidson NE, Esteva FJ, Gonzalez-Angulo AM, Krop I, Levinson J, Lin NU, Modi S, Patt DA, Perez EA, Perlmutter J, Ramakrishna N, Winer EP. Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. Journal Of Clinical Oncology 2014, 32: 2078-2099. PMID: 24799465, PMCID: PMC6076031, DOI: 10.1200/jco.2013.54.0948.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAnastrozoleAntibodies, Monoclonal, HumanizedAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsClinical Trials as TopicComorbidityDocetaxelDrug Administration ScheduleEvidence-Based MedicineFemaleHealth Status DisparitiesHealthcare DisparitiesHumansLapatinibLetrozoleMaytansineMolecular Targeted TherapyNitrilesQuinazolinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSocieties, MedicalTaxoidsTrastuzumabTreatment OutcomeTriazolesUnited StatesConceptsAdvanced breast cancerHuman epidermal growth factor receptorSecond-line treatmentProgression-free survivalFirst-line treatmentBreast cancerPFS benefitT-DM1Epidermal growth factor receptorEndocrine therapyGrowth factor receptorSystemic therapyEstrogen receptor-positive/progesterone receptor-positive breast cancerAdvanced human epidermal growth factor receptorHER2-positive advanced breast cancerProgesterone receptor-positive breast cancerClinical Oncology Clinical Practice GuidelineClinical congestive heart failureStandard first-line therapyPositive advanced breast cancerLeft ventricular ejection fractionOncology Clinical Practice GuidelineReceptor-positive breast cancerThird-line settingFirst-line therapy
2012
Phase I Pharmacologic and Pharmacodynamic Study of the Gamma Secretase (Notch) Inhibitor MK-0752 in Adult Patients With Advanced Solid Tumors
Krop I, Demuth T, Guthrie T, Wen PY, Mason WP, Chinnaiyan P, Butowski N, Groves MD, Kesari S, Freedman SJ, Blackman S, Watters J, Loboda A, Podtelezhnikov A, Lunceford J, Chen C, Giannotti M, Hing J, Beckman R, LoRusso P. Phase I Pharmacologic and Pharmacodynamic Study of the Gamma Secretase (Notch) Inhibitor MK-0752 in Adult Patients With Advanced Solid Tumors. Journal Of Clinical Oncology 2012, 30: 2307-2313. PMID: 22547604, DOI: 10.1200/jco.2011.39.1540.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsClinical benefitDose levelsSolid tumorsCommon drug-related toxicitiesGene signatureObjective complete responsePreliminary antitumor efficacyWeekly dose levelMaximum-tolerated doseDose-proportional mannerDrug-related toxicityHigh-grade gliomasHighest dose levelStable diseaseWeekly dosingAdult patientsComplete responseOral inhibitorNotch signalingCombination trialsNovel agentsPharmacodynamic studiesPatientsNotch pathway activation
2010
Phase I Study of Trastuzumab-DM1, an HER2 Antibody-Drug Conjugate, Given Every 3 Weeks to Patients With HER2-Positive Metastatic Breast Cancer
Krop IE, Beeram M, Modi S, Jones SF, Holden SN, Yu W, Girish S, Tibbitts J, Yi JH, Sliwkowski MX, Jacobson F, Lutzker SG, Burris HA. Phase I Study of Trastuzumab-DM1, an HER2 Antibody-Drug Conjugate, Given Every 3 Weeks to Patients With HER2-Positive Metastatic Breast Cancer. Journal Of Clinical Oncology 2010, 28: 2698-2704. PMID: 20421541, DOI: 10.1200/jco.2009.26.2071.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBiopsy, NeedleBone NeoplasmsBreast NeoplasmsDose-Response Relationship, DrugDrug Administration ScheduleFemaleFollow-Up StudiesHalf-LifeHumansImmunoconjugatesImmunohistochemistryLiver NeoplasmsLung NeoplasmsMaximum Tolerated DoseMaytansineMiddle AgedNeoplasm StagingPatient SelectionReceptor, ErbB-2Risk AssessmentSurvival AnalysisThrombocytopeniaTrastuzumabTreatment OutcomeConceptsMaximum-tolerated doseAdvanced HER2-positive breast cancerHER2-positive breast cancerTrastuzumab-DM1Breast cancerAdverse eventsCommon drug-related adverse eventsHER2-positive metastatic breast cancerDrug-related adverse eventsHER2 antibody-drug conjugatesClinical benefit rateConfirmed response rateSubstantial clinical activityTrastuzumab-based therapyMetastatic breast cancerHER2-positive cellsAntibody-drug conjugatesMeasurable diseaseNeuropathy eventsElevated transaminasesCardiac effectsDose modificationMetastatic diseaseObjective responseReversible toxicity