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
2016
Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study
Tolaney SM, Nechushtan H, Ron IG, Schöffski P, Awada A, Yasenchak CA, Laird AD, O’Keeffe B, Shapiro GI, Winer EP. Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study. Breast Cancer Research And Treatment 2016, 160: 305-312. PMID: 27714541, PMCID: PMC5065609, DOI: 10.1007/s10549-016-4001-y.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalOverall survivalStable diseaseMBC patientsWeek 12Common grade 3/4 adverse eventsOverall median progression-free survivalGrade 3/4 adverse eventsMedian progression-free survivalSolid Tumors version 1.0Metastatic breast cancer patientsOral tyrosine kinase inhibitorResultsForty-five patientsDisease control rateMedian overall survivalPalmar-plantar erythrodysesthesiaResponse Evaluation CriteriaMetastatic breast carcinomaBreast cancer patientsTyrosine kinase inhibitorsCabozantinib monotherapyDiscontinuation studyPrimary endpointRespiratory failure
2013
A Phase I dose-escalation study of the VEGFR inhibitor tivozanib hydrochloride with weekly paclitaxel in metastatic breast cancer
Mayer EL, Scheulen ME, Beckman J, Richly H, Duarte A, Cotreau MM, Strahs AL, Agarwal S, Steelman L, Winer EP, Dickler MN. A Phase I dose-escalation study of the VEGFR inhibitor tivozanib hydrochloride with weekly paclitaxel in metastatic breast cancer. Breast Cancer Research And Treatment 2013, 140: 331-339. PMID: 23868188, DOI: 10.1007/s10549-013-2632-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFemaleHumansMiddle AgedNeoplasm MetastasisPaclitaxelPhenylurea CompoundsProtein Kinase InhibitorsQuinolinesVascular Endothelial Growth Factor Receptor-1ConceptsMetastatic breast cancerTyrosine kinase inhibitorsWeekly paclitaxelPaclitaxel 90Breast cancerPhase I dose-escalation studyI dose-escalation studyVascular endothelial growth factor receptor 1Activity of tivozanibSafety/tolerabilityGrade 3/4 toxicitiesPeripheral sensory neuropathyPhase Ib studyDose-escalation studyResponse Evaluation CriteriaSelective tyrosine kinase inhibitorVEGFR-TKI treatmentSolid Tumors responseGrowth factor receptor 1Influence of paclitaxelFactor receptor 1Stable diseaseMBC patientsPartial responseProgressive disease
2010
Cardiac Toxicity From Systemic Cancer Therapy: A Comprehensive Review
Curigliano G, Mayer EL, Burstein HJ, Winer EP, Goldhirsch A. Cardiac Toxicity From Systemic Cancer Therapy: A Comprehensive Review. Progress In Cardiovascular Diseases 2010, 53: 94-104. PMID: 20728696, DOI: 10.1016/j.pcad.2010.05.006.Peer-Reviewed Original ResearchConceptsCardiac adverse effectsCardiac toxicityCardiovascular toxicityNew drug developmentLeft ventricular ejection fraction declineVentricular ejection fraction declineAdverse effectsClassic chemotherapy agentsEjection fraction declinePotential cardiovascular toxicityRare serious complicationsNovel biologic agentsSignificant cardiac dysfunctionAcute coronary syndromeCongestive heart failureLong-term complicationsTypes of malignanciesSystemic cancer therapyLife-threatening eventsCancer therapyTyrosine kinase inhibitorsDrug developmentCardiovascular safetyCoronary syndromeBiologic agents
2009
Use of BIBW 2992, a Novel Irreversible EGFR/HER1 and HER2 Tyrosine Kinase Inhibitor To Treat Patients with HER2-Positive Metastatic Breast Cancer after Failure of Treatment with Trastuzumab.
Hickish T, Wheatley D, Lin N, Carey L, Houston S, Mendelson D, Solca F, Uttenreuther-Fischer M, Jones H, Winer E. Use of BIBW 2992, a Novel Irreversible EGFR/HER1 and HER2 Tyrosine Kinase Inhibitor To Treat Patients with HER2-Positive Metastatic Breast Cancer after Failure of Treatment with Trastuzumab. Cancer Research 2009, 69: 5060-5060. DOI: 10.1158/0008-5472.sabcs-09-5060.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerEpidermal growth factor receptorPhase II studyMetastatic breast cancerBIBW 2992Partial responseBreast cancerGrowth factor receptorII studyEastern Cooperative Oncology Group performance statusSingle-arm phase II studyHER2-positive breast cancer patientsTrastuzumab-resistant cell linesHER2-positive breast cancerHER2 tyrosine kinase inhibitorAdequate organ functionCutaneous adverse eventsEarly clinical responseObjective response rateFactor receptorBreast cancer patientsFailure of treatmentTyrosine kinase inhibitorsEligible patientsMeasurable diseaseUse of BIBW 2992, a novel irreversible EGFR/HER2 tyrosine kinase inhibitor (TKI), to treat patients with HER2-positive metastatic breast cancer after failure of treatment with trastuzumab
Hickish T, Wheatley D, Lin N, Carey L, Houston S, Mendelson D, Solca F, Uttenreuther-Fischer M, Jones H, Winer E. Use of BIBW 2992, a novel irreversible EGFR/HER2 tyrosine kinase inhibitor (TKI), to treat patients with HER2-positive metastatic breast cancer after failure of treatment with trastuzumab. Journal Of Clinical Oncology 2009, 27: 1023-1023. DOI: 10.1200/jco.2009.27.15_suppl.1023.Peer-Reviewed Original ResearchHER2-positive metastatic breast cancerPhase II studyMetastatic breast cancerBIBW 2992Tyrosine kinase inhibitorsPartial responseBreast cancerEpidermal growth factor receptorStable diseaseAdverse eventsII studyDisease progressionTumor assessmentOpen-label single-arm phase II studySide effectsEastern Cooperative Oncology Group performance statusSingle-arm phase II studyHER2-positive breast cancer patientsDual epidermal growth factor receptorArm phase II studyTrastuzumab-resistant cell linesEGFR/HER2 tyrosine kinase inhibitorHER2-positive breast cancerHER2 tyrosine kinase inhibitorAdequate organ functionA phase I study of vandetanib and metronomic chemotherapy in advanced breast cancer.
Mayer E, Isakoff S, Hannagan K, Savoie J, Beckman J, Klement G, Gelman R, Winer E, Burstein H. A phase I study of vandetanib and metronomic chemotherapy in advanced breast cancer. Cancer Research 2009, 69: 906. DOI: 10.1158/0008-5472.sabcs-906.Peer-Reviewed Original ResearchAdvanced breast cancerDose-escalation cohortsAbnormal hepatic functionVascular endothelial growth factorBreast cancerMetronomic chemotherapyHepatic functionContinuous low-dose oral cyclophosphamideLow-dose oral cyclophosphamideSequential dose-escalation cohortsStage IV breast cancerOral tyrosine kinase inhibitorGrade 3 eventsOral combination therapyPrior chemotherapy regimensStable brain metastasesModest clinical activityAnti-angiogenic treatmentTyrosine kinase inhibitorsEndothelial growth factorEpidermal growth factor receptorEligible patientsGrowth factor receptorMeasurable diseaseModerate hypertension
2004
New targets for therapy in breast cancer: Small molecule tyrosine kinase inhibitors
Lin NU, Winer EP. New targets for therapy in breast cancer: Small molecule tyrosine kinase inhibitors. Breast Cancer Research 2004, 6: 204. PMID: 15318926, PMCID: PMC549180, DOI: 10.1186/bcr919.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsBreast cancerSmall molecule tyrosine kinase inhibitorsMolecule tyrosine kinase inhibitorsKinase inhibitorsErbB familyPredictive markerClinical dataReceptor signal transduction pathwaySmall molecule inhibitorsTumor sensitivityTumor growthReceptor tyrosine kinasesNew targetsCritical pathwaysMolecule inhibitorsCancerPotential crosstalkInhibitorsTyrosine kinaseSignal transduction pathwaysRational combinationBroad spectrumTransduction pathwaysMalignancy