2021
Updated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB).
Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey L, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Zhang C, Winer E. Updated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB). Journal Of Clinical Oncology 2021, 39: 1043-1043. DOI: 10.1200/jco.2021.39.15_suppl.1043.Peer-Reviewed Original ResearchMetastatic breast cancerBrain metastasesOverall survivalTyrosine kinase inhibitorsBreast cancerPlacebo armAnalysis of OSOral tyrosine kinase inhibitorECOG performance statusPlacebo-controlled trialTotal study populationKaplan-Meier timeHER2CLIMB trialMeaningful prolongationMetastatic HER2Study medicationTolerability assessmentsMetastatic settingAdverse eventsDose modificationHazard ratioLast patientPerformance statusDisease progressionStudy population
2020
Management of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB).
Okines A, Paplomata E, Wahl T, Wright G, Sutherland S, Jakobsen E, Valdes F, Chan A, Clark A, Conlin A, Lustberg M, Specht J, Pluard T, Zhu X, Krop I, Gelmon K, Slamon D, Ramos J, An G, Hamilton E. Management of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB). Journal Of Clinical Oncology 2020, 38: 1043-1043. DOI: 10.1200/jco.2020.38.15_suppl.1043.Peer-Reviewed Original ResearchAdverse eventsMedian timeControl armBreast cancerExposure-adjusted incidence ratesElevated liver enzymesMetastatic breast cancerCases of diarrheaMedian durationDose modificationTx groupIncidence rateLiver enzymesHigh incidenceDiarrheaTucatinibFirst onsetCapecitabineTrastuzumabHER2Significant inhibitionBilirubinLonger durationCycle 1Patients
2012
A phase 1 study of weekly dosing of trastuzumab emtansine (T‐DM1) in patients with advanced human epidermal growth factor 2–positive breast cancer
Beeram M, Krop IE, Burris HA, Girish SR, Yu W, Lu MW, Holden SN, Modi S. A phase 1 study of weekly dosing of trastuzumab emtansine (T‐DM1) in patients with advanced human epidermal growth factor 2–positive breast cancer. Cancer 2012, 118: 5733-5740. PMID: 22648179, DOI: 10.1002/cncr.27622.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdverse eventsT-DM1Breast cancerTrastuzumab emtansineObjective partial tumor responseTreatment-related adverse eventsClinical benefit rateDose-escalation studyPartial tumor responsePhase 1 studyTotal trastuzumabDose modificationMedian durationWeekly doseWeekly dosingAdditional patientsTumor responseBenefit rateHuman epidermal growth factorEpidermal growth factorPatientsGrowth factorAntitumor activity
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