2024
A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer
Giordano A, Kumthekar P, Jin Q, Kurt B, Ren S, Li T, Leone J, Mittendorf E, Pereslete A, Sharp L, Davis R, DiLullo M, Tayob N, Mayer E, Winer E, Tolaney S, Lin N. A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer. Clinical Cancer Research 2024, 30: of1-of10. PMID: 39226397, PMCID: PMC11528201, DOI: 10.1158/1078-0432.ccr-24-1161.Peer-Reviewed Original ResearchHER2-positive breast cancer brain metastasesBreast cancer brain metastasesClinical benefit rateCancer brain metastasesCentral nervous systemCNS responseBrain metastasesOverall response rateOverall survivalAny-grade adverse eventsEffective systemic therapy optionsNeuro-Oncology Brain MetastasesHER2-positive breast cancerIntracranial partial responseSystemic therapy optionsPhase II studyPhase II trialCNS ORRRANO-BMDose delaysPartial responseII studyPrimary endpointHigh-doseBenefit rateNeratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022 ☆
Freedman R, Heiling H, Li T, Trapani D, Tayob N, Smith K, Davis R, Pereslete A, DeMeo M, Cotter C, Chen W, Parsons H, Santa-Maria C, Van Poznak C, Moy B, Brufsky A, Melisko M, O’Sullivan C, Ashai N, Rauf Y, Nangia J, Burns R, Savoie J, Wolff A, Winer E, Rimawi M, Krop I, Lin N. Neratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022 ☆. Annals Of Oncology 2024, 35: 993-1002. PMID: 38977064, DOI: 10.1016/j.annonc.2024.07.245.Peer-Reviewed Original ResearchHER2-positive breast cancer brain metastasesBreast cancer brain metastasesT-DM1Ado-trastuzumab emtansineCentral nervous systemOverall survivalCNS objective response rateEfficacy of neratinibT-DM1 exposureObjective response rateCancer brain metastasesPhase II studyMedian OSRANO-BMBrain MetastasesSlow accrualIntracranial activityII studyPrimary endpointPreclinical dataCohort 4Response assessmentTreatment optionsNeratinibPatients
2022
Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases
Kabraji S, Ni J, Sammons S, Li T, Van Swearingen AED, Wang Y, Pereslete A, Hsu L, DiPiro PJ, Lascola C, Moore H, Hughes M, Raghavendra AS, Gule-Monroe M, Murthy RK, Winer EP, Anders CK, Zhao JJ, Lin NU. Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases. Clinical Cancer Research 2022, 29: 174-182. PMID: 36074155, PMCID: PMC9811155, DOI: 10.1158/1078-0432.ccr-22-1138.Peer-Reviewed Original ResearchConceptsBreast cancer brain metastasesActive brain metastasesObjective response rateCNS objective response rateCancer brain metastasesBrain metastasesT-DXdPatient-derived xenograftsPDX modelsCohort studyTrastuzumab deruxtecanClinical efficacyClinical trialsHER2-positive breast cancer brain metastasesMetastatic HER2-positive breast cancerResponse rateMulti-institutional cohort studyHER2-positive breast cancerRetrospective multi-institutional cohort studyOrthotopic patient-derived xenograftsRetrospective cohort studyProspective clinical trialsSubset of patientsCentral nervous system activityPivotal clinical trialsp16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
Ni J, Kabraji S, Xie S, Wang Y, Pan P, He X, Liu Z, Leone JP, Long HW, Brown MA, Winer EP, Dillon DAR, Lin NU, Zhao JJ. p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases. Nature Communications 2022, 13: 1473. PMID: 35304445, PMCID: PMC8933392, DOI: 10.1038/s41467-022-29081-2.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsBrain metastasesMetastatic HER2-positive breast cancerBiomarker-driven clinical trialsBreast cancer brain metastasesHER2-positive breast cancerOrthotopic patient-derived xenograftsMajority of HER2Cancer brain metastasesCDK4/6 inhibitionProtein immunohistochemistryClinical trialsBreast cancerHER2Tumor suppressor p16INK4aPatientsMetastasisBCBMAbemaciclibTucatinibXenograftsImmunohistochemistryCancerCDK4/6Trials
2021
SYST-06. PHASE II TRIAL OF PAXALISIB (GDC-0084) IN COMBINATION WITH TRASTUZUMAB FOR PATIENTS WITH HER2-POSITIVE BREAST CANCER BRAIN METASTASES (BCBM)
Leone J, Tayob N, Pereslete A, Ligibel J, Parsons H, Bi W, Zhao J, Winer E, Lin N. SYST-06. PHASE II TRIAL OF PAXALISIB (GDC-0084) IN COMBINATION WITH TRASTUZUMAB FOR PATIENTS WITH HER2-POSITIVE BREAST CANCER BRAIN METASTASES (BCBM). Neuro-Oncology Advances 2021, 3: iv9-iv9. DOI: 10.1093/noajnl/vdab112.034.Peer-Reviewed Original ResearchBreast cancer brain metastasesObjective response rateCohort BCohort ACNS metastasesPrimary endpointHER2-positive breast cancer brain metastasesNeuro-Oncology Brain Metastases criteriaCentral nervous system metastasesHER2-positive breast cancerPatient-derived xenografts (PDX) modelsPhase II cohortNervous system metastasesPhase II studyCancer brain metastasesPhase II trialPI3K/Akt/mTORPatient-reported outcomesPI3KBrain-penetrant inhibitorAkt/mTORMetastasis (TNM) criteriaBrain metastasesII trialMetastasis resection
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 MRIPhase I dose-escalation trial of tucatinib in combination with trastuzumab in patients with HER2-positive breast cancer brain metastases
Filho O, Leone JP, Li T, Tan-Wasielewski Z, Trippa L, Barry WT, Younger J, Lawler E, Walker L, Freedman RA, Tolaney SM, Krop I, Winer EP, Lin NU. Phase I dose-escalation trial of tucatinib in combination with trastuzumab in patients with HER2-positive breast cancer brain metastases. Annals Of Oncology 2020, 31: 1231-1239. PMID: 32461105, DOI: 10.1016/j.annonc.2020.05.014.Peer-Reviewed Original ResearchConceptsClinical benefit rateHER2-positive brain metastasesAlanine aminotransferase elevationCohort ABrain metastasesCohort BAminotransferase elevationBreast cancerHER2-positive breast cancer brain metastasesPhase I dose-escalation trialMedian progression-free survivalBreast cancer brain metastasesCommon dose-limiting toxicityI dose-escalation trialHER2-positive breast cancerCombination of tucatinibSecondary end pointsCancer brain metastasesDose-escalation trialProgression-free survivalDose-limiting toxicityMetastatic breast cancerBrain radiationObjective responseIntracranial activityGenomic profiling of breast cancer brain metastases reveals targetable alterations.
Kabraji S, Spurr L, Hughes M, Li Y, Leone J, Garrido-Castro A, Barroso-Sousa R, Files J, Kirkner G, Johnson B, Winer E, Cherniack A, Lin N. Genomic profiling of breast cancer brain metastases reveals targetable alterations. Journal Of Clinical Oncology 2020, 38: 2525-2525. DOI: 10.1200/jco.2020.38.15_suppl.2525.Peer-Reviewed Original ResearchBreast cancer brain metastasesTumor mutation burdenCancer brain metastasesBrain metastasesTargetable alterationsGenomic alterationsDana-Farber Cancer InstituteTwo-sided Fisher's exact testPIK3CA/PTENActionable genomic alterationsFisher's exact testNumber alterationsTwo-sided MannWhitney U testPrimary tumorMetastatic tumorsMutation burdenERBB2 amplificationCancer InstituteMultiple comparison correctionCancer-related genesExact testCopy number alterationsGenomic profilingU test
2019
A phase II study of cabozantinib alone or in combination with trastuzumab in breast cancer patients with brain metastases
Leone JP, Duda DG, Hu J, Barry WT, Trippa L, Gerstner ER, Jain RK, Tan S, Lawler E, Winer EP, Lin NU, Tolaney SM. A phase II study of cabozantinib alone or in combination with trastuzumab in breast cancer patients with brain metastases. Breast Cancer Research And Treatment 2019, 179: 113-123. PMID: 31541381, DOI: 10.1007/s10549-019-05445-z.Peer-Reviewed Original ResearchConceptsBreast cancer brain metastasesObjective response rateCNS objective response ratePhase II studyCohort 2Cohort 1BCBM patientsBrain metastasesII studyCohort 3Central nervous system (CNS) objective response rateMost common grade 3/4 adverse eventsCommon grade 3/4 adverse eventsSingle-arm phase II studyGrade 3/4 adverse eventsSecondary objectiveTolerability of cabozantinibWhole brain radiationCancer brain metastasesProgression-free survivalBreast cancer patientsTumor blood volumeCabozantinib 60RECIST 1.1STie-2Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022
Freedman RA, Gelman RS, Agar NYR, Santagata S, Randall EC, Lopez B, Connolly RM, Dunn IF, Van Poznak CH, Anders CK, Melisko ME, Silvestri K, Cotter CM, Componeschi KP, Marte JM, Moy B, Blackwell KL, Puhalla SL, Ibrahim N, Moynihan TJ, Nangia J, Tung N, Burns R, Rimawi MF, Krop IE, Wolff AC, Winer EP, Lin NU, Consortium T. Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022. Clinical Breast Cancer 2019, 20: 145-151.e2. PMID: 31558424, PMCID: PMC7035200, DOI: 10.1016/j.clbc.2019.07.011.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAntineoplastic Combined Chemotherapy ProtocolsBrainBrain NeoplasmsBreastBreast NeoplasmsChemotherapy, AdjuvantCraniotomyDrug Administration ScheduleFemaleHumansMiddle AgedNeoadjuvant TherapyPilot ProjectsQuinolinesReceptor, ErbB-2Tissue DistributionTreatment OutcomeConceptsCentral nervous system penetrationCerebrospinal fluidBrain metastasesStudy treatmentDisease progressionHER2-positive breast cancer brain metastasesHER2-positive metastatic breast cancerHER2-positive brain metastasesBreast cancer brain metastasesGrade 3 diarrheaCancer brain metastasesMetastatic breast cancerCentral nervous systemResected tumor tissueBlood-based analysesNeratinib monotherapyPostoperative cyclesParenchymal tumorsStudy protocolBreast cancerTumor histopathologyPatientsNervous systemSmall cohortSurgical tissuesTRLS-03. PHASE II TRIAL OF GDC-0084 IN COMBINATION WITH TRASTUZUMAB FOR PATIENTS WITH HER2-POSITIVE BREAST CANCER BRAIN METASTASES (BCBM)
Leone J, Trippa L, Milisits L, Andrews C, Ligibel J, Parsons H, Bi W, Zhao J, Winer E, Lin N. TRLS-03. PHASE II TRIAL OF GDC-0084 IN COMBINATION WITH TRASTUZUMAB FOR PATIENTS WITH HER2-POSITIVE BREAST CANCER BRAIN METASTASES (BCBM). Neuro-Oncology Advances 2019, 1: i9-i9. PMCID: PMC7213424, DOI: 10.1093/noajnl/vdz014.036.Peer-Reviewed Original ResearchBreast cancer brain metastasesObjective response rateCohort BCohort ACNS metastasesPrimary endpointHER2-positive breast cancer brain metastasesNeuro-Oncology Brain Metastases criteriaCentral nervous system metastasesHER2-positive breast cancerPatient-derived xenografts (PDX) modelsPhase II cohortNervous system metastasesPhase II studyCancer brain metastasesPhase II trialPI3K/Akt/mTORPatient-reported outcomesPI3KBrain-penetrant inhibitorAkt/mTORCombination of GDCMetastasis (TNM) criteriaBrain metastasesII trialTBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
Freedman RA, Gelman RS, Anders CK, Melisko ME, Parsons HA, Cropp AM, Silvestri K, Cotter CM, Componeschi KP, Marte JM, Connolly RM, Moy B, Van Poznak CH, Blackwell KL, Puhalla SL, Jankowitz RC, Smith KL, Ibrahim N, Moynihan TJ, O’Sullivan C, Nangia J, Niravath P, Tung N, Pohlmann PR, Burns R, Rimawi MF, Krop IE, Wolff AC, Winer EP, Lin NU, . TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases. Journal Of Clinical Oncology 2019, 37: jco.18.01511. PMID: 30860945, PMCID: PMC6494354, DOI: 10.1200/jco.18.01511.Peer-Reviewed Original ResearchConceptsCNS objective response rateObjective response rateHER2-positive breast cancer brain metastasesBreast cancer brain metastasesCancer brain metastasesBrain metastasesBreast cancerCommon grade 3 toxicitiesHER2-positive brain metastasesMedian progression-free survivalHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Human epidermal growth factor receptorEfficacy of HER2Non-CNS progressionGrade 3 toxicityPrimary end pointPhase II trialProgression-free survivalGrowth factor receptor 2Positive breast cancerProgressive neurologic signsEvidence-based treatmentsFactor receptor 2Epidermal growth factor receptor
2018
A phase II study of cabozantinib (cabo) alone or in combination with trastuzumab (T) in patients (pts) with breast cancer brain metastases (BCBM).
Leone J, Hu J, Barry W, Duda D, Gerstner E, Jain R, Tan S, Lawler E, Winer E, Lin N, Tolaney S. A phase II study of cabozantinib (cabo) alone or in combination with trastuzumab (T) in patients (pts) with breast cancer brain metastases (BCBM). Journal Of Clinical Oncology 2018, 36: 1026-1026. DOI: 10.1200/jco.2018.36.15_suppl.1026.Peer-Reviewed Original ResearchDrug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain?
Kabraji S, Ni J, Lin NU, Xie S, Winer EP, Zhao JJ. Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain? Clinical Cancer Research 2018, 24: 1795-1804. PMID: 29437794, PMCID: PMC5899637, DOI: 10.1158/1078-0432.ccr-17-3351.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsAntineoplastic Combined Chemotherapy ProtocolsBlood-Brain BarrierBrain NeoplasmsBreast NeoplasmsClinical Studies as TopicDisease Models, AnimalDrug DevelopmentDrug Evaluation, PreclinicalDrug Resistance, NeoplasmFemaleHumansMiceModels, BiologicalReceptor, ErbB-2Translational Research, BiomedicalTreatment OutcomeXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesHER2-positive breast cancer brain metastasesTreatment of BCBMHER2-positive breast cancerHER2-targeting drugsInadequate drug penetrationBrain metastasis modelCancer brain metastasesCentral nervous systemClin Cancer ResDrug resistance mechanismsBrain metastasesFirst metastasisEffective therapyCommon siteBreast cancerMetastasis modelPharmacodynamic dataNervous systemTranslational research paradigmDrug penetrationCancer ResDrug sensitivityPatientsDrug development
2017
TBCRC 022: Phase II trial of neratinib + capecitabine for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer brain metastases (BCBM).
Freedman R, Gelman R, Melisko M, Anders C, Moy B, Blackwell K, Connolly R, Niravath P, Van Poznak C, Puhalla S, Farooq S, Cropp A, Cotter C, Liu M, Krop I, Nangia J, Tung N, Wolff A, Winer E, Lin N. TBCRC 022: Phase II trial of neratinib + capecitabine for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer brain metastases (BCBM). Journal Of Clinical Oncology 2017, 35: 1005-1005. DOI: 10.1200/jco.2017.35.15_suppl.1005.Peer-Reviewed Original ResearchBreast cancer brain metastasesObjective response rateCombination of neratinibCentral nervous system (CNS) objective response rateCNS objective response rateNeurologic signs/symptomsGrade 3 toxicityGrade 4 toxicityMedian age 51Cancer brain metastasesPhase II trialSigns/symptomsEvidence-based treatmentsNon-CNS lesionsCNS progressionPrior lapatinibPrior WBRTPrimary endpointProtocol therapyBrain metastasesII trialCNS lesionsNew lesionsMedian numberBrain MRI
2016
Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases
Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nature Medicine 2016, 22: 723-726. PMID: 27270588, PMCID: PMC4938731, DOI: 10.1038/nm.4120.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAminopyridinesAnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsBreast NeoplasmsCarrier ProteinsCaspase 3Cell Cycle ProteinsDNA RepairDrug Resistance, NeoplasmDrug Therapy, CombinationEukaryotic Initiation FactorsEverolimusFemaleGene Expression ProfilingGenomic InstabilityHumansImmunohistochemistryKi-67 AntigenMagnetic Resonance ImagingMechanistic Target of Rapamycin Complex 1MiceMice, SCIDMolecular Targeted TherapyMorpholinesMultiprotein ComplexesNeoplasm TransplantationPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationReceptor, ErbB-2Remission InductionTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesCancer brain metastasesBrain metastasesHER2-positive breast cancer brain metastasesOrthotopic patient-derived xenograftsPI3KPatient-derived xenograftsDurable remissionsTherapeutic responseMouse modelCombined inhibitionCombination inhibitionMetastasisInhibitionRemissionXenograftsMiceTranslational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
Freedman RA, Gelman RS, Wefel JS, Melisko ME, Hess KR, Connolly RM, Van Poznak CH, Niravath PA, Puhalla SL, Ibrahim N, Blackwell KL, Moy B, Herold C, Liu MC, Lowe A, Agar NY, Ryabin N, Farooq S, Lawler E, Rimawi MF, Krop IE, Wolff AC, Winer EP, Lin NU. Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases. Journal Of Clinical Oncology 2016, 34: 945-952. PMID: 26834058, PMCID: PMC5070554, DOI: 10.1200/jco.2015.63.0343.Peer-Reviewed Original ResearchConceptsObjective response rateWhole brain radiotherapyBrain metastasesBreast cancerHER2-positive breast cancer brain metastasesCNS objective response rateHER2-positive brain metastasesMedian progression-free survivalNeurologic signs/symptomsPrevious whole-brain radiotherapyBreast cancer brain metastasesHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Human epidermal growth factor receptorCNS-directed therapyNon-CNS progressionNon-target lesionsOpen-label trialCancer brain metastasesPhase II trialProgression-free survivalGrowth factor receptor 2Positive breast cancerSigns/symptoms
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
2013
A phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer brain metastases
Lin NU, Freedman RA, Ramakrishna N, Younger J, Storniolo AM, Bellon JR, Come SE, Gelman RS, Harris GJ, Henderson MA, MacDonald SM, Mahadevan A, Eisenberg E, Ligibel JA, Mayer EL, Moy B, Eichler AF, Winer EP. A phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer brain metastases. Breast Cancer Research And Treatment 2013, 142: 405-414. PMID: 24197661, DOI: 10.1007/s10549-013-2754-0.Peer-Reviewed Original ResearchConceptsWhole brain radiotherapyDose-limiting toxicityObjective response rateHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Growth factor receptor 2Positive breast cancerCentral nervous diseasesBrain metastasesFactor receptor 2Brain radiotherapyBreast cancerReceptor 2CNS objective response rateBreast cancer brain metastasesHigher objective response rateCareful safety monitoringCancer brain metastasesGrade 3 rashPre-defined criteriaEligible patientsEvaluable patientsLapatinib 1000Pulmonary emboliDose escalationPhase II trial of carboplatin (C) and bevacizumab (BEV) in patients (pts) with breast cancer brain metastases (BCBM).
Lin N, Gelman R, Younger W, Sohl J, Freedman R, Sorensen A, Bullitt E, Harris G, Morganstern D, Schneider B, Krop I, Winer E. Phase II trial of carboplatin (C) and bevacizumab (BEV) in patients (pts) with breast cancer brain metastases (BCBM). Journal Of Clinical Oncology 2013, 31: 513-513. DOI: 10.1200/jco.2013.31.15_suppl.513.Peer-Reviewed Original ResearchBreast cancer brain metastasesCNS responseDay 1CNS objective response rateNon-target lesionsObjective response rateAnti-edema effectCancer brain metastasesPhase II trialProgressive neurologic signsStandard brain MRINon-CNS diseasesMultiple tumor typesPrior lapatinibPrior trastuzumabRECIST 1.0Steroid dosePrimary endpointProtocol therapyBrain metastasesFirst doseII trialCNS lesionsOverall survivalPartial response