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 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
2016
Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases
Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nature Medicine 2016, 22: 723-726. PMID: 27270588, PMCID: PMC4938731, DOI: 10.1038/nm.4120.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAminopyridinesAnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsBreast NeoplasmsCarrier ProteinsCaspase 3Cell Cycle ProteinsDNA RepairDrug Resistance, NeoplasmDrug Therapy, CombinationEukaryotic Initiation FactorsEverolimusFemaleGene Expression ProfilingGenomic InstabilityHumansImmunohistochemistryKi-67 AntigenMagnetic Resonance ImagingMechanistic Target of Rapamycin Complex 1MiceMice, SCIDMolecular Targeted TherapyMorpholinesMultiprotein ComplexesNeoplasm TransplantationPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationReceptor, ErbB-2Remission InductionTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesCancer brain metastasesBrain metastasesHER2-positive breast cancer brain metastasesOrthotopic patient-derived xenograftsPI3KPatient-derived xenograftsDurable remissionsTherapeutic responseMouse modelCombined inhibitionCombination inhibitionMetastasisInhibitionRemissionXenograftsMice
2013
Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry
Kluk MJ, Ashworth T, Wang H, Knoechel B, Mason EF, Morgan EA, Dorfman D, Pinkus G, Weigert O, Hornick JL, Chirieac LR, Hirsch M, Oh DJ, South AP, Leigh IM, Pourreyron C, Cassidy AJ, DeAngelo DJ, Weinstock DM, Krop IE, Dillon D, Brock JE, Lazar AJ, Peto M, Cho RJ, Stoeck A, Haines BB, Sathayanrayanan S, Rodig S, Aster JC. Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry. PLOS ONE 2013, 8: e67306. PMID: 23825651, PMCID: PMC3688991, DOI: 10.1371/journal.pone.0067306.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorHeterograftsHumansImmunohistochemistryMiceMutationReceptor, Notch1ConceptsCell lymphomaNotch1 activationNOTCH1 mutationsPeripheral T-cell lymphomaNon-small cell lung carcinomaLymphoblastic leukemia/lymphomaTriple-negative breast cancerLarge B-cell lymphomaSelection of patientsChronic lymphocytic leukemia cellsT-cell lymphomaCell lung carcinomaNegative breast cancerChronic lymphocytic leukemiaLeukemia/lymphomaB-cell lymphomaMantle cell lymphomaB-cell tumorsRole of Notch1Lymphocytic leukemia cellsLymph nodesAngioimmunoblastic lymphomaCell tumorsClinical trialsOvarian carcinoma
2011
Phase I/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy
Morrow PK, Wulf GM, Ensor J, Booser DJ, Moore JA, Flores PR, Xiong Y, Zhang S, Krop IE, Winer EP, Kindelberger DW, Coviello J, Sahin AA, Nuñez R, Hortobagyi GN, Yu D, Esteva FJ. Phase I/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy. Journal Of Clinical Oncology 2011, 29: 3126-3132. PMID: 21730275, PMCID: PMC3157979, DOI: 10.1200/jco.2010.32.2321.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDisease-Free SurvivalEverolimusFemaleHumansImmunohistochemistryKaplan-Meier EstimateMiddle AgedNeoplasm MetastasisPTEN PhosphohydrolaseReceptor, ErbB-2Salvage TherapySirolimusTOR Serine-Threonine KinasesTrastuzumabConceptsHER2-overexpressing metastatic breast cancerMetastatic breast cancerProgression-free survivalCombination of everolimusTrastuzumab-based therapyPTEN lossBreast cancerPhase I/II studyMedian progression-free survivalDana-Farber Cancer InstituteTexas MD Anderson Cancer CenterMD Anderson Cancer CenterBeth Israel Deaconess Medical CenterClinical benefit ratePersistent stable diseaseAnderson Cancer CenterDownstream mammalian targetDaily everolimusNonhematologic toxicityStable diseaseII studyOverall survivalPartial responseHER2 overexpressingClinical benefit
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
2008
Short Preoperative Treatment With Erlotinib Inhibits Tumor Cell Proliferation in Hormone Receptor–Positive Breast Cancers
Guix M, de Matos Granja N, Meszoely I, Adkins TB, Wieman BM, Frierson KE, Sanchez V, Sanders ME, Grau AM, Mayer IA, Pestano G, Shyr Y, Muthuswamy S, Calvo B, Krontiras H, Krop IE, Kelley MC, Arteaga CL. Short Preoperative Treatment With Erlotinib Inhibits Tumor Cell Proliferation in Hormone Receptor–Positive Breast Cancers. Journal Of Clinical Oncology 2008, 26: 897-906. PMID: 18180460, DOI: 10.1200/jco.2007.13.5939.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsCell ProliferationChemotherapy, AdjuvantErbB ReceptorsErlotinib HydrochlorideFemaleHumansImmunohistochemistryIn Situ Nick-End LabelingKi-67 AntigenMiceMice, NudeMiddle AgedNeoadjuvant TherapyNeoplasm StagingNeoplasms, Hormone-DependentProtein Kinase InhibitorsProtein-Tyrosine KinasesQuinazolinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSignal TransductionTandem Mass SpectrometryTreatment OutcomeXenograft Model Antitumor AssaysConceptsTumor cell proliferationBreast cancerPreoperative treatmentCell proliferationHormone receptor-positive breast cancerP-S6P-AktEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinibHormone receptor-positive cancersReceptor-positive breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2ER-positive breast cancerP-EGFRTyrosine kinase inhibitor erlotinibTriple-negative breast cancerP-MAPKImmediate preoperative periodUntreated breast cancerGrowth factor receptor 2Day of surgeryInvasive breast cancerReceptor-positive cancersTriple-negative cancersKinase inhibitor erlotinib