2024
Neratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022 ☆
Freedman R, Heiling H, Li T, Trapani D, Tayob N, Smith K, Davis R, Pereslete A, DeMeo M, Cotter C, Chen W, Parsons H, Santa-Maria C, Van Poznak C, Moy B, Brufsky A, Melisko M, O’Sullivan C, Ashai N, Rauf Y, Nangia J, Burns R, Savoie J, Wolff A, Winer E, Rimawi M, Krop I, Lin N. Neratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022 ☆. Annals Of Oncology 2024, 35: 993-1002. PMID: 38977064, DOI: 10.1016/j.annonc.2024.07.245.Peer-Reviewed Original ResearchHER2-positive breast cancer brain metastasesBreast cancer brain metastasesT-DM1Ado-trastuzumab emtansineCentral nervous systemOverall survivalCNS objective response rateEfficacy of neratinibT-DM1 exposureObjective response rateCancer brain metastasesPhase II studyMedian OSRANO-BMBrain MetastasesSlow accrualIntracranial activityII studyPrimary endpointPreclinical dataCohort 4Response assessmentTreatment optionsNeratinibPatients
2012
Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody–drug conjugate in development for the treatment of HER2-positive cancer
Girish S, Gupta M, Wang B, Lu D, Krop IE, Vogel CL, Burris III HA, LoRusso PM, Yi JH, Saad O, Tong B, Chu YW, Holden S, Joshi A. Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody–drug conjugate in development for the treatment of HER2-positive cancer. Cancer Chemotherapy And Pharmacology 2012, 69: 1229-1240. PMID: 22271209, PMCID: PMC3337408, DOI: 10.1007/s00280-011-1817-3.Peer-Reviewed Original ResearchConceptsSingle-agent T-DM1Anti-therapeutic antibodiesT-DM1 exposureTotal trastuzumabT-DM1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Standard noncompartmental approachT-DM1 pharmacokineticsGrowth factor receptor 2Key adverse eventsMetastatic breast cancerHER2-positive cancersStable thioether linkerConcentrations of transaminasesFactor receptor 2Enzyme-linked immunosorbent assayEnzyme-linked immunosorbentHER2 extracellular domainAntibody-drug conjugatesEvaluable patientsPrior therapyClinical responseAdverse events
2009
A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients with advanced HER2+ breast cancer.
Krop I, Mita M, Burris H, Birkner M, Girish S, Tibbitts J, Holden S, Lutzker S, Modi S. A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients with advanced HER2+ breast cancer. Cancer Research 2009, 69: 3136. DOI: 10.1158/0008-5472.sabcs-3136.Peer-Reviewed Original ResearchTrastuzumab-DM1Advanced HER2Antibody-drug conjugatesBreast cancerChemotherapy regimenCycle 1 day 1HER2 antibody-drug conjugatesFirst antibody-drug conjugatePhase IActivity of trastuzumabGrade 4 thrombocytopeniaReversible transaminase elevationT-DM1 exposureDose-escalation studyPhase II trialMeasurable diseaseQ3W dosingTransaminase elevationEscalation studyII trialPartial responseWeekly dosingCardiac toxicityTumor responseClinical trials