2023
Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases
Lin N, Murthy R, Abramson V, Anders C, Bachelot T, Bedard P, Borges V, Cameron D, Carey L, Chien A, Curigliano G, DiGiovanna M, Gelmon K, Hortobagyi G, Hurvitz S, Krop I, Loi S, Loibl S, Mueller V, Oliveira M, Paplomata E, Pegram M, Slamon D, Zelnak A, Ramos J, Feng W, Winer E. Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases. JAMA Oncology 2023, 9: 197-205. PMID: 36454580, PMCID: PMC9716438, DOI: 10.1001/jamaoncol.2022.5610.Peer-Reviewed Original ResearchConceptsErbB2-positive metastatic breast cancerMetastatic breast cancerPlacebo-combination groupPositive metastatic breast cancerNew brain lesionsBrain metastasesOverall survivalSubgroup analysisBrain lesionsBreast cancerIntracranial progression-free survivalPlacebo-controlled clinical trialIntracranial objective response rateStable brain metastasesMedian overall survivalObjective response rateProgression-free survivalExploratory subgroup analysisGreater clinical benefitCNS-PFSHER2CLIMB trialIntracranial outcomesFirst progressionMedian ageClinical benefit
2020
Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB).
Lin N, Murthy R, Anders C, Borges V, Hurvitz S, Loi S, Abramson V, Bedard P, Oliveira M, Zelnak A, DiGiovanna M, Bachelot T, Chien A, O'Regan R, Wardley A, Müller V, Carey L, McGoldrick S, An G, Winer E. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). Journal Of Clinical Oncology 2020, 38: 1005-1005. DOI: 10.1200/jco.2020.38.15_suppl.1005.Peer-Reviewed Original ResearchMetastatic breast cancerProgression-free survivalObjective response rateBrain metastasesOverall survivalCNS-PFSControl armSecond progressionEfficacy analysisBrain progressionLocal treatmentBreast cancerProlongation of PFSMedian progression-free survivalExploratory efficacy analysesMedian CNS-PFSMedian overall survivalBaseline brain MRIHER2 kinase inhibitorDeath overallRECIST 1.1Study therapyFree survivalInvestigator's evaluationIC disease
2013
Phase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer.
James E, Chung G, Sowers N, Clark M, Lilian R, Abraham G, Chmael S, Cappiello M, DiGiovanna M, Hofstatter E, Sanft T, Israel G, Pusztai L, Harris L, Abu-Khalaf M. Phase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer. Journal Of Clinical Oncology 2013, 31: 154-154. DOI: 10.1200/jco.2013.31.26_suppl.154.Peer-Reviewed Original ResearchDose-expansion phaseGrade 3 non-hematological toxicityGrade 4 febrile neutropeniaCycle-1 DLTGrade 3 fatigueGrade 3/4 toxicitiesGrade 4 neutropeniaGrade 4 thrombocytopeniaMedian age 51Non-hematological toxicitiesObjective response rateAdvanced breast cancerDose-escalation phaseModest clinical activityHDAC inhibitor vorinostatClinical trial informationHistone deacetylase inhibitorsFebrile neutropeniaStable diseaseObjective responsePrior linesHematological toxicityTreatment delayClinical activityBreast cancerPhase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer.
James E, Chung G, DiGiovanna M, Sanft T, Hofstatter E, Sowers N, Clark M, Lilian R, Chmael S, Cappiello M, Abraham G, Israel G, Pusztai L, Harris L, Abu-Khalaf M. Phase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer. Journal Of Clinical Oncology 2013, 31: 2587-2587. DOI: 10.1200/jco.2013.31.15_suppl.2587.Peer-Reviewed Original ResearchDose-expansion phaseGrade 3 non-hematological toxicityTGFB pathwayGrade 4 febrile neutropeniaCycle-1 DLTGrade 3 fatigueGrade 3/4 toxicitiesGrade 4 neutropeniaGrade 4 thrombocytopeniaMedian age 51Non-hematological toxicitiesObjective response rateAdvanced breast cancerDose-escalation phaseModest clinical activityBiomarkers of responseHDAC inhibitor vorinostatClinical trial informationHistone deacetylase inhibitorsFebrile neutropeniaStable diseaseObjective responsePrior linesHematological toxicityTreatment delay