2021
Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis
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, Feng W, Winer E. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Annals Of Oncology 2021, 33: 321-329. PMID: 34954044, DOI: 10.1016/j.annonc.2021.12.005.Peer-Reviewed Original ResearchConceptsProgression-free survivalMetastatic breast cancerPlacebo-combination groupOverall survivalCombination groupBreast cancerHER2CLIMB trialBrain metastasesMedian durationSafety outcomesPrimary analysisFinal overall survival analysisHuman epidermal growth factor receptor 2 positive metastatic breast cancerPositive metastatic breast cancerMeaningful survival benefitMedian overall survivalPlacebo-controlled trialOverall study populationOverall survival analysisFinal OSMetastatic HER2Placebo combinationAdverse eventsLast patientPrespecified subgroupsUpdated 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
A phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC).
Waks A, Keenan T, Li T, Tayob N, Wulf G, Richardson E, Mittendorf E, Overmoyer B, Krop I, Winer E, Van Allen E, Agudo J, Tolaney S. A phase Ib study of pembrolizumab (pembro) plus trastuzumab emtansine (T-DM1) for metastatic HER2+ breast cancer (MBC). Journal Of Clinical Oncology 2020, 38: 1046-1046. DOI: 10.1200/jco.2020.38.15_suppl.1046.Peer-Reviewed Original ResearchObjective response rateProgression-free survivalAdverse eventsT-DM1PD-L1 combined positive scoreTumor-infiltrating lymphocyte (TIL) statusClinical benefit rateDose-finding cohortMedian age 54Phase 2 dosePhase Ib studyCombined positive scoreAnti-PD1 antibodyPhase 1 trialDe-escalation designEligible patientsLymphocyte statusMetastatic HER2Expansion cohortOral mucositisPrimary endpointSecondary endpointsAntitumor immunityImmune signaturesPrior lines