2016
A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function
Li C, Agarwal P, Gibiansky E, Jin J, Dent S, Gonçalves A, Nijem I, Strasak A, Harle-Yge M, Chernyukhin N, LoRusso P, Girish S. A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function. Clinical Pharmacokinetics 2016, 56: 1069-1080. PMID: 27995530, DOI: 10.1007/s40262-016-0496-y.Peer-Reviewed Original ResearchConceptsNormal hepatic functionModerate hepatic impairmentHepatic impairmentMetastatic breast cancerHepatic functionTrastuzumab emtansineBreast cancerCycle 1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Phase I pharmacokinetic studyHuman epidermal growth factor receptorChild-Pugh criteriaMild hepatic impairmentT-DM1 3.6T-DM1 exposureGrowth factor receptor 2I pharmacokinetic studyFactor receptor 2Epidermal growth factor receptorGrowth factor receptorModerate cohortBaseline albuminT-DM1
2013
Trastuzumab emtansine (T-DM1) in previously treated HER2-positive metastatic breast cancer (MBC): Results from an expanded access study.
Yardley D, Krop I, LoRusso P, Robert N, Mayer M, Abidoye O, Lai C, Yoo B, Perez E. Trastuzumab emtansine (T-DM1) in previously treated HER2-positive metastatic breast cancer (MBC): Results from an expanded access study. Journal Of Clinical Oncology 2013, 31: 166-166. DOI: 10.1200/jco.2013.31.26_suppl.166.Peer-Reviewed Original ResearchMetastatic breast cancerObjective response rateHER2-positive metastatic breast cancerT-DM1Investigator-assessed objective response rateMedian cumulative anthracycline doseAccess StudyCumulative anthracycline doseCytotoxic agent DM1HER2-directed agentsMost common gradeUS multicenter studyNew safety signalsRate of gradeConventional clinical trialsAnthracycline doseGrade AEsMBC therapyMeasurable diseaseMedian LVEFPrior anthracyclineSecondary endpointsMUGA scanCardiac dysfunctionMulticenter study
2012
Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.
Modi S, Elias A, LoRusso P, Samant M, Guardino E, Althaus B, Krop I. Results from a phase Ib study of trastuzumab emtansine (T-DM1), paclitaxel (T), and pertuzumab (P) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab. Journal Of Clinical Oncology 2012, 30: 528-528. DOI: 10.1200/jco.2012.30.15_suppl.528.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerMetastatic breast cancerT-DM1Prior systemic therapyPhase Ib studyPhase II studyDose-escalation studySingle-agent activityDuration of responseDose escalation schemeFuture clinical trialsDLT criteriaII studyMedian ageSystemic therapyExtension trialPreclinical dataTrastuzumab emtansineClinical trialsMedian numberToxicity CriteriaBreast cancerIb studyPhase IbQ3w
2011
Pharmacokinetic and pathophysiologic covariates influencing treatment outcomes with T-DM1 in patients with HER2-positive metastatic breast cancer (MBC).
Gupta M, LoRusso P, Burris H, Wang B, Joshi A, Tong Y, Chu Y, Girish S. Pharmacokinetic and pathophysiologic covariates influencing treatment outcomes with T-DM1 in patients with HER2-positive metastatic breast cancer (MBC). Journal Of Clinical Oncology 2011, 29: 633-633. DOI: 10.1200/jco.2011.29.15_suppl.633.Peer-Reviewed Original Research
2009
A Phase II Study of Trastuzumab-DM1 (T-DM1), a Novel HER2 Antibody–Drug Conjugate, in HER2+ Metastatic Breast Cancer (MBC) Patients Previously Treated with Conventional Chemotherapy, Lapatinib and Trastuzumab.
Krop I, LoRusso P, Miller K, Modi S, Yardley D, Rodriguez G, Agresta S, Zheng M, Amler L, Rugo H. A Phase II Study of Trastuzumab-DM1 (T-DM1), a Novel HER2 Antibody–Drug Conjugate, in HER2+ Metastatic Breast Cancer (MBC) Patients Previously Treated with Conventional Chemotherapy, Lapatinib and Trastuzumab. Cancer Research 2009, 69: 5090-5090. DOI: 10.1158/0008-5472.sabcs-09-5090.Peer-Reviewed Original ResearchPopulation Pharmacokinetics of Trastuzumab-DM1, a First-in-Class HER2 Antibody-Drug Conjugate Given Every 3 Weeks (q3w) and Weekly (qw) to Patients with HER2-Positive Metastatic Breast Cancer (MBC).
LoRusso P, Girish S, Burris H, Beeram M, Vukelja S, Modi S, Yi J, Wang B, Saad O, Gupta M. Population Pharmacokinetics of Trastuzumab-DM1, a First-in-Class HER2 Antibody-Drug Conjugate Given Every 3 Weeks (q3w) and Weekly (qw) to Patients with HER2-Positive Metastatic Breast Cancer (MBC). Cancer Research 2009, 69: 5099-5099. DOI: 10.1158/0008-5472.sabcs-09-5099.Peer-Reviewed Original ResearchMetastatic breast cancerHER2-positive metastatic breast cancerHER2 antibody-drug conjugatesPhase II trialT-DM1Antibody-drug conjugatesII trialClinical factorsInter-individual variabilityTumor burdenIndividual patientsCovariate analysisPK parametersPK dataPK modelOngoing phase II trialSubsequent phase II trialTwo-compartment linear modelPhase I trialPopulation PK modelPopulation pharmacokinetic modelMultiple dose levelsConcentration-time dataAvailable PK dataPK parameter values