2020
Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases
Leone JP, Emblem KE, Weitz M, Gelman RS, Schneider BP, Freedman RA, Younger J, Pinho MC, Sorensen AG, Gerstner ER, Harris G, Krop IE, Morganstern D, Sohl J, Hu J, Kasparian E, Winer EP, Lin NU. Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases. Breast Cancer Research 2020, 22: 131. PMID: 33256829, PMCID: PMC7706261, DOI: 10.1186/s13058-020-01372-w.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBrainBrain NeoplasmsBreastBreast NeoplasmsCarboplatinFemaleGenotyping TechniquesHumansKaplan-Meier EstimateMagnetic Resonance ImagingMiddle AgedPolymorphism, Single NucleotideProgression-Free SurvivalTrastuzumabVascular Endothelial Growth Factor AConceptsProgression-free survivalBreast cancer brain metastasesEarly MRI changesCancer brain metastasesBrain metastasesOverall survivalMRI changesBreast cancerEastern Cooperative Oncology Group performance statusDay 1Cycle 1 day 1Cycle 1 day 8Median progression-free survivalWorse progression-free survivalRegimen warrants further investigationDurable objective responsesECOG PS 1Efficacy of bevacizumabHER2-positive diseaseProgressive brain metastasesResultsThirty-eight patientsMedian overall survivalObjective response ratePhase II trialContrast-enhanced brain MRI
2014
TBCRC 018: phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases
Anders C, Deal AM, Abramson V, Liu MC, Storniolo AM, Carpenter JT, Puhalla S, Nanda R, Melhem-Bertrandt A, Lin NU, Kelly Marcom P, Van Poznak C, Stearns V, Melisko M, Smith JK, Karginova O, Parker J, Berg J, Winer EP, Peterman A, Prat A, Perou CM, Wolff AC, Carey LA. TBCRC 018: phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases. Breast Cancer Research And Treatment 2014, 146: 557-566. PMID: 25001612, PMCID: PMC4112043, DOI: 10.1007/s10549-014-3039-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBenzamidesBrain NeoplasmsCamptothecinDrug-Related Side Effects and Adverse ReactionsFemaleHumansIrinotecanMiddle AgedNeoplasm StagingReceptor, ErbB-2Survival AnalysisTriple Negative Breast NeoplasmsVascular Endothelial Growth Factor AConceptsTriple-negative breast cancerClinical benefit rateBrain metastasesOverall survivalResponse rateTriple negative breast cancer brain metastasisCommon grade 3/4 adverse eventsAdvanced triple-negative breast cancerGrade 3/4 adverse eventsIntracranial clinical benefit rateBreast cancer brain metastasesGrade 3/4 diarrheaIntracranial response ratesProgressive brain metastasesMedian overall survivalPhase II studyPrimary end pointCancer brain metastasesHalf of patientsHealth-related qualityBRCA germline mutationsTreatment-refractory diseaseBlood-brain barrierNegative breast cancerGermline BRCA1/2 status
2011
Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases
Lin NU, Eierman W, Greil R, Campone M, Kaufman B, Steplewski K, Lane SR, Zembryki D, Rubin SD, Winer EP. Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases. Journal Of Neuro-Oncology 2011, 105: 613-620. PMID: 21706359, DOI: 10.1007/s11060-011-0629-y.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerProgressive brain metastasesObjective response rateBrain metastasesTopotecan armBreast cancerHER2-positive breast cancer brain metastasesCentral nervous system progressionBreast cancer brain metastasesRandomized phase II studyCombination of lapatinibPhase II studyCancer brain metastasesEfficacy of lapatinibStandard radiation therapyLack of efficacyNon-CNS lesionsExcess toxicityCapecitabine armRefractory settingCranial radiotherapyPrimary endpointSteroid requirementsII studyObjective response
2009
Multicenter Phase II Study of Lapatinib in Patients with Brain Metastases from HER2-Positive Breast Cancer
Lin N, Diéras V, Paul D, Lossignol D, Christodoulou C, Stemmler H, Roché H, Liu M, Greil R, Ciruelos E, Loibl S, Gori S, Wardley A, Yardley D, Brufsky A, Blum J, Rubin S, Dharan B, Steplewski K, Zembryki D, Oliva C, Roychowdhury D, Paoletti P, Winer E. Multicenter Phase II Study of Lapatinib in Patients with Brain Metastases from HER2-Positive Breast Cancer. Clinical Cancer Research 2009, 15: 1452-1459. PMID: 19228746, DOI: 10.1158/1078-0432.ccr-08-1080.Peer-Reviewed Original ResearchConceptsBrain metastasesBreast cancerObjective responseVolumetric reductionCNS lesionsNeurologic signsCentral nervous system progressionMulticenter phase II studySmall phase 2 trialHER2-positive breast cancerCombination of lapatinibExtra-CNS diseaseProgressive brain metastasesPhase II studyPrimary end pointPhase 2 trialProgression-free survivalThird of patientsProgressive neurologic signsMajor clinical challengeCNS metastasesCranial radiationEligible patientsEvaluable patientsPrior trastuzumab
2008
Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Lin NU, Carey LA, Liu MC, Younger J, Come SE, Ewend M, Harris GJ, Bullitt E, Van den Abbeele AD, Henson JW, Li X, Gelman R, Burstein HJ, Kasparian E, Kirsch DG, Crawford A, Hochberg F, Winer EP. Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer. Journal Of Clinical Oncology 2008, 26: 1993-1999. PMID: 18421051, PMCID: PMC4524351, DOI: 10.1200/jco.2007.12.3588.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorNon-CNS sitesPrimary end pointBrain metastasesBreast cancerGrowth factor receptorEnd pointAdverse eventsObjective responseAdvanced human epidermal growth factor receptor 2Human epidermal growth factor receptor 2Epidermal growth factor receptor 2Human epidermal growth factor receptorBrain tumor burdenProgressive brain metastasesRefractory brain metastasesCommon adverse eventsSecondary end pointsPhase II trialResponse Evaluation CriteriaEfficacy of lapatinibFactor receptorGrowth factor receptor 2Metastatic brain lesionsPositive breast cancer
2007
EGF105084, a phase II study of lapatinib for brain metastases in patients (pts) with HER2+ breast cancer following trastuzumab (H) based systemic therapy and cranial radiotherapy (RT)
Lin N, Dieras V, Paul D, Lossignol D, Christodoulou C, Laessig D, Roché H, Zembryki D, Oliva C, Winer E. EGF105084, a phase II study of lapatinib for brain metastases in patients (pts) with HER2+ breast cancer following trastuzumab (H) based systemic therapy and cranial radiotherapy (RT). Journal Of Clinical Oncology 2007, 25: 1012-1012. DOI: 10.1200/jco.2007.25.18_suppl.1012.Peer-Reviewed Original ResearchNeurological signs/symptomsCNS diseaseCranial radiotherapyBreast cancerBrain metastasesSystemic therapyInitial phase II trialDose of steroidsECOG PS 0Extra-CNS diseaseIndependent radiology reviewProgressive brain metastasesPhase II studyPhase II trialLarge multicenter trialsSigns/symptomsCNS disease progressionAnalysis of efficacyPreliminary dataEligible ptsH therapyPo bidRefractory settingAccrual goalII trial
2006
Phase II trial of lapatinib for brain metastases in patients with HER2+ breast cancer
Lin N, Carey L, Liu M, Younger J, Come S, Bullitt E, Van Den Abbeele A, Li X, Hochberg F, Winer E. Phase II trial of lapatinib for brain metastases in patients with HER2+ breast cancer. Journal Of Clinical Oncology 2006, 24: 503-503. DOI: 10.1200/jco.2006.24.18_suppl.503.Peer-Reviewed Original ResearchBrain metastasesBreast cancerObjective responsePrimary endpointCNS lesionsCNS diseaseCentral nervous system metastasesVolumetric declinesCentral radiology reviewProgressive brain metastasesNervous system metastasesPhase II trialEfficacy of lapatinibMetastatic breast cancerFDG-PET scansMean age 52Analysis of QOLCommon AEsEligible patientsMeasurable diseasePo bidII trialPrior radiationRECIST criteriaSecondary endpoints