2024
Tucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in HER2+ breast cancer: TBCRC049 phase 2 study results.
O'Brien B, Murthy R, Berry D, Singareeka Raghavendra A, Gule-Monroe M, Johnson J, Schwartz-Gomez J, Topletz-Erickson A, Lobbous M, Melisko M, Morikawa A, Ferguson S, de Groot J, Krop I, Valero V, Rimawi M, Wolff A, Tripathy D, Lin N, Stringer-Reasor E. Tucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in HER2+ breast cancer: TBCRC049 phase 2 study results. Journal Of Clinical Oncology 2024, 42: 2018-2018. DOI: 10.1200/jco.2024.42.16_suppl.2018.Peer-Reviewed Original ResearchHER2+ breast cancerLeptomeningeal metastasesPatient-reported outcomesBreast cancerObjective responseClinical examCSF cytologyEvidence of clinically meaningful benefitHER2-targeted tyrosine kinase inhibitorsMedian time to CNS progressionMetastatic HER2+ breast cancerKarnofsky performance status >Treatment of leptomeningeal metastasesAbnormal CSF cytologyPerformance status >Targeted neurological deficitsMDASI-BTPhase 2 studyTyrosine kinase inhibitorsClinically meaningful benefitPre-specified timepointsPreliminary efficacy dataCNS progressionMedian OSCNS metastases
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 populationPharmacokinetic (PK) analyses in CSF and plasma from TBCRC049, an ongoing trial to assess the safety and efficacy of the combination of tucatinib, trastuzumab and capecitabine for the treatment of leptomeningeal metastasis (LM) in HER2 positive breast cancer.
Stringer-Reasor E, O'Brien B, Topletz-Erickson A, White J, Lobbous M, Riley K, Childress J, LaMaster K, Melisko M, Morikawa A, De Groot J, Krop I, Valero V, Rimawi M, Wolff A, Tripathy D, Lin N, Murthy R. Pharmacokinetic (PK) analyses in CSF and plasma from TBCRC049, an ongoing trial to assess the safety and efficacy of the combination of tucatinib, trastuzumab and capecitabine for the treatment of leptomeningeal metastasis (LM) in HER2 positive breast cancer. Journal Of Clinical Oncology 2021, 39: 1044-1044. DOI: 10.1200/jco.2021.39.15_suppl.1044.Peer-Reviewed Original ResearchLeptomeningeal metastasesBrain metastasesBreast cancerPharmacokinetic analysisPhase 2 single-arm studyHER2-positive breast cancerCombination of tucatinibNew brain metastasesSingle-arm studyPositive breast cancerTyrosine kinase inhibitorsHigh interindividual variabilityMetastatic HER2Accrual goalEligible patientsMetastatic settingPrimary endpointOverall survivalOmmaya reservoirOngoing trialsPlasma concentrationsCapecitabinePatientsDay 1PK samplesA011801 (CompassHER2 RD): Postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer.
O'Sullivan C, Ballman K, McCall L, Zemla T, Weiss A, Mitchell M, Blinder V, Tung N, Irvin W, Lee M, Goetz M, Symmans W, Borges V, Krop I, Partridge A, Carey L. A011801 (CompassHER2 RD): Postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer. Journal Of Clinical Oncology 2021, 39: tps595-tps595. DOI: 10.1200/jco.2021.39.15_suppl.tps595.Peer-Reviewed Original ResearchInvasive disease-free survivalEarly breast cancerTyrosine kinase inhibitorsAdjuvant T-DM1Neoadjuvant therapyPathologic complete responseDisease-free survivalResidual diseaseT-DM1Postoperative chemotherapyAdjuvant radiationBreast cancerHER2-positive invasive breast cancerBrain metastasis-free survivalBreast cancer-free survivalPathologic lymph node statusDistant recurrence-free survivalClinical stage IIInvasive residual diseasePost-neoadjuvant therapyCancer-free survivalDe-escalation trialsLymph node statusRecurrence-free survivalSelective tyrosine kinase inhibitor
2018
Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial
Borges VF, Ferrario C, Aucoin N, Falkson C, Khan Q, Krop I, Welch S, Conlin A, Chaves J, Bedard PL, Chamberlain M, Gray T, Vo A, Hamilton E. Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial. JAMA Oncology 2018, 4: 1214-1220. PMID: 29955792, PMCID: PMC6143009, DOI: 10.1001/jamaoncol.2018.1812.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAntineoplastic Combined Chemotherapy ProtocolsArea Under CurveBreast NeoplasmsDiarrheaDrug Administration ScheduleFatigueFemaleHumansKaplan-Meier EstimateMaytansineMiddle AgedNauseaNeoplasm MetastasisProtein Kinase InhibitorsReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsTrastuzumabConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdo-trastuzumab emtansineT-DM1Breast cancerTyrosine kinase inhibitorsBrain metastasesAdverse eventsClinical trialsToxic reactionsDose-limiting toxic reactionHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Phase 1b clinical trialGrowth factor receptor 2ERBB2/HER2-positive breast cancerPreliminary antitumor activityTreatment of patientsSpecific tyrosine kinase inhibitorYears of ageDrug-drug interactionsFactor receptor 2Hepatic transaminitisHER2 therapy
2017
CMET-25. PROGRESSION-FREE SURVIVAL (PFS) AND SITE OF FIRST PROGRESSION IN HER2+ METASTATIC BREAST CANCER PATIENTS WITH OR WITHOUT BRAIN METASTASES: A POOLED ANALYSIS OF TUCATINIB PHASE I STUDIES
Hamilton E, Moulder S, Ferrario C, Conlin A, Krop I, Chamberlain M, Gray T, Borges V. CMET-25. PROGRESSION-FREE SURVIVAL (PFS) AND SITE OF FIRST PROGRESSION IN HER2+ METASTATIC BREAST CANCER PATIENTS WITH OR WITHOUT BRAIN METASTASES: A POOLED ANALYSIS OF TUCATINIB PHASE I STUDIES. Neuro-Oncology 2017, 19: vi44-vi44. PMCID: PMC5692086, DOI: 10.1093/neuonc/nox168.173.Peer-Reviewed Original ResearchProgression-free survivalBaseline brain metastasesMetastatic breast cancerBrain metastasesMedian progression-free survivalMetastatic breast cancer patientsPhase 1b studyProgressive brain metastasesStable brain metastasesSite of relapseIncidence of progressionSignificant neurologic morbidityUntreated brain metastasesBreast cancer patientsTyrosine kinase inhibitorsBM cohortHER2 therapyHER2CLIMB trialPrior HER2Neurologic morbidityDurable responsesFirst progressionSystemic metastasesCombination therapyPatient cohort