2021
Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial
Tolaney SM, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Briccetti F, Schneider B, Garrett AM, Marcom K, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu M, Ruddy K, Zheng Y, Rosenberg SM, Gelber RD, Trippa L, Barry W, DeMeo M, Burstein H, Partridge A, Winer EP, Krop I. Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial. Journal Of Clinical Oncology 2021, 39: 2375-2385. PMID: 34077270, DOI: 10.1200/jco.20.03398.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDisease-Free SurvivalFemaleHumansMiddle AgedNeoplasm StagingPaclitaxelTrastuzumabConceptsInvasive disease-free survivalT-DM1Breast cancerStage IStage I HER2-positive breast cancerHER2-positive breast cancerHuman epidermal growth factor receptorAdjuvant T-DM1Co-primary objectivesDisease-free survivalPatient-reported outcomesEpidermal growth factor receptorGrowth factor receptorProtocol therapyAnalysis populationTrastuzumab emtansineClinical trialsRelevant toxicityPatientsFactor receptorLess toxicityWeeksTrastuzumabCancerPaclitaxelUpdated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological Complete Response to Pertuzumab and Trastuzumab in Breast Cancer
Connolly RM, Leal JP, Solnes L, Huang CY, Carpenter A, Gaffney K, Abramson V, Carey LA, Liu MC, Rimawi M, Specht J, Storniolo AM, Valero V, Vaklavas C, Krop IE, Winer EP, Camp M, Miller RS, Wolff AC, Cimino-Mathews A, Park BH, Wahl RL, Stearns V. Updated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological Complete Response to Pertuzumab and Trastuzumab in Breast Cancer. Journal Of Clinical Oncology 2021, 39: 2247-2256. PMID: 33999652, PMCID: PMC8260904, DOI: 10.1200/jco.21.00280.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantFemaleFluorodeoxyglucose F18HumansMiddle AgedNeoadjuvant TherapyPositron Emission Tomography Computed TomographyPredictive Value of TestsRadiopharmaceuticalsReceptor, ErbB-2Time FactorsTrastuzumabTreatment OutcomeUnited StatesConceptsPositron emission tomography-computed tomographyFluorodeoxyglucose positron emission tomography-computed tomographyHER2-positive breast cancerEmission tomography-computed tomographyPathologic complete responseTomography-computed tomographyStandardized uptake valueBreast cancerComplete responseUptake valuePercent changeOne-sided type ITumor maximum standardized uptake valueHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Maximum standardized uptake valuePathological complete responseGrowth factor receptor 2Median percent reductionPositive breast cancerTailoring of therapyLean body massReceiver operator characteristic analysisFactor receptor 2Operator characteristic analysisImpact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab
Filho OM, Viale G, Stein S, Trippa L, Yardley DA, Mayer IA, Abramson VG, Arteaga CL, Spring LM, Waks AG, Wrabel E, DeMeo MK, Bardia A, Dell'Orto P, Russo L, King TA, Polyak K, Michor F, Winer EP, Krop IE. Impact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab. Cancer Discovery 2021, 11: candisc.1557.2020. PMID: 33941592, PMCID: PMC8598376, DOI: 10.1158/2159-8290.cd-20-1557.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFemaleHumansMiddle AgedNeoadjuvant TherapyReceptor, ErbB-2TrastuzumabTreatment OutcomeConceptsHER2-positive breast cancerHER2 heterogeneityBreast cancerEarly-stage HER2-positive breast cancerHER2-positive early-stage breast cancerTherapeutic resistancePathologic complete response rateEarly-stage breast cancerNeoadjuvant clinical trialsComplete response rateSubset of patientsHER2 therapyPretreatment biopsiesEvaluable casesCure rateT-DM1Trastuzumab emtansineClinical trialsTreatment strategiesTreatment responseTreatment selectionResponse rateRelated commentaryTherapyIssue featureThe impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2-positive breast cancer
Janiszewska M, Stein S, Filho O, Eng J, Kingston NL, Harper NW, Rye IH, Alečković M, Trinh A, Murphy KC, Marangoni E, Cristea S, Oakes B, Winer EP, Krop I, Russnes HG, Spellman PT, Bucher E, Hu Z, Chin K, Gray JW, Michor F, Polyak K. The impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2-positive breast cancer. JCI Insight 2021, 6: e147617. PMID: 33886505, PMCID: PMC8262355, DOI: 10.1172/jci.insight.147617.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDNA Copy Number VariationsDrug Resistance, NeoplasmEpithelial CellsFemaleFibroblastsHumansMacrophagesMiddle AgedMutationNeoplasm TransplantationReceptor, ErbB-2TrastuzumabTumor MicroenvironmentVesicular Transport ProteinsConceptsBreast cancerTherapeutic resistanceHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Patient-derived xenograft modelsLymphatic vessel endothelial hyaluronan receptorHER2-targeted therapiesGrowth factor receptor 2Impact of tumorFibroblastic reticular cellsFactor receptor 2Tumor epithelial cellsIntratumor heterogeneityDivergent cellular phenotypesResistance-conferring mutationsClinical outcomesPIK3CA mutationsTreatment responseClinical challengeDifferent therapiesFrequency of cellsXenograft modelReceptor 2Stromal determinants
2020
Antitumor 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 ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalBreast NeoplasmsCamptothecinFemaleHumansImmunoconjugatesImmunohistochemistryMiddle AgedNeoplasm MetastasisReceptor, ErbB-2TrastuzumabConceptsInterstitial 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 toxicityA 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
Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study
Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C, Sugihara M, Shahidi J, Yver A, Modi S. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. The Lancet Oncology 2019, 20: 816-826. PMID: 31047803, DOI: 10.1016/s1470-2045(19)30097-x.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBreast NeoplasmsCamptothecinFemaleFollow-Up StudiesHumansImmunoconjugatesMaximum Tolerated DoseMiddle AgedPrognosisReceptor, ErbB-2Salvage TherapySurvival RateTissue DistributionTrastuzumabConceptsHER2-positive breast cancerTreatment-emergent adverse eventsAdvanced-stage breast cancerTrastuzumab emtansine treatmentTrastuzumab deruxtecanPhase 1 trialBreast cancerAdverse eventsProgressive diseaseSerious treatment-emergent adverse eventsWorse treatment-emergent adverse eventsAdvanced HER2-positive breast cancerSolid tumorsTopoisomerase I inhibitor payloadFrequent grade 3Grade 3 eventsTreatment-related deathsManageable safety profileAdvanced solid tumorsMultiple-dose studyPhase 1 studyInterstitial lung diseaseWithdrawal of consentWhite blood cellsYears of age
2018
Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis
Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, Tolaney SM. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncology 2018, 4: 173-182. PMID: 28973656, PMCID: PMC5838579, DOI: 10.1001/jamaoncol.2017.3064.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalCell Cycle CheckpointsEndocrine GlandsEndocrine System DiseasesHumansImmunotherapyIncidenceNeoplasmsProtein Kinase InhibitorsRandomized Controlled Trials as TopicConceptsPD-1 inhibitorsCTLA-4 inhibitorsPD-L1 inhibitorsPrimary adrenal insufficiencyInsulin-deficient diabetesAdverse eventsCombination therapyEndocrine dysfunctionSystematic reviewAdrenal insufficiencyPD-1Clinical trialsDifferent immune checkpoint inhibitorsIncidence of AEsImmune checkpoint inhibitorsAdvanced solid tumorsEndocrine adverse eventsRisk of hyperthyroidismSuch adverse eventsPreferred Reporting ItemsRandom-effects modelGrade hypothyroidismInhibitor regimensMDX-010Checkpoint inhibitors
2016
Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer
Varadan V, Gilmore H, Miskimen KL, Tuck D, Parsai S, Awadallah A, Krop IE, Winer EP, Bossuyt V, Somlo G, Abu-Khalaf MM, Fenton MA, Sikov W, Harris L. Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer. Clinical Cancer Research 2016, 22: 3249-3259. PMID: 26842237, PMCID: PMC5439498, DOI: 10.1158/1078-0432.ccr-15-2021.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminsAntineoplastic Agents, ImmunologicalBiomarkers, TumorB-LymphocytesBreast NeoplasmsFemaleGene Expression ProfilingHumansImmunity, InnateLymphocyte ActivationMacrophagesMiddle AgedNeoadjuvant TherapyPaclitaxelProgrammed Cell Death 1 ReceptorReceptor, ErbB-2T-Lymphocytes, Helper-InducerTrastuzumabTreatment OutcomeConceptsPathologic complete responseBreast cancerImmune indicesBrief exposureFollicular helper T (Tfh) cell signatureHER2-positive breast cancerPD-1 positivitySingle-agent trastuzumabTrastuzumab-based therapyT cell activityT-cell signatureImmune cell infiltrationTumor core biopsiesImmune cell activationPreoperative trastuzumabNab-paclitaxelAntitumor immunityImmune signaturesPCR rateComplete responseMulticenter trialPD-1Cell infiltrationCore biopsyIntrinsic subtypes