2019
Complications associated with immunotherapy for brain metastases.
Tran TT, Jilaveanu LB, Omuro A, Chiang VL, Huttner A, Kluger HM. Complications associated with immunotherapy for brain metastases. Current Opinion In Neurology 2019, 32: 907-916. PMID: 31577604, PMCID: PMC7398556, DOI: 10.1097/wco.0000000000000756.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBrain NeoplasmsHumansImmunologic FactorsImmunotherapyNeoplasm MetastasisNeoplasm Recurrence, LocalNeurotoxicity SyndromesConceptsBrain metastasesNeurologic toxicityImmune therapyPhase 2 clinical trialCheckpoint inhibitor therapyImmune checkpoint inhibitorsMultiple phase 2 clinical trialsTreatment-related morbidityBrain metastatic diseaseSymptomatic edemaCheckpoint inhibitorsAdverse eventsDurable responsesMedian survivalMetastatic diseaseInhibitor therapyMore patientsIntracranial activityPatient groupRadiation necrosisClinical trialsTherapy trialsMultidisciplinary teamMetastasisPatients
2018
Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805
Jilaveanu LB, Puligandla M, Weiss SA, Wang X, Zito C, Flaherty KT, Boeke M, Neumeister V, Camp RL, Adeniran A, Pins M, Manola J, DiPaola RS, Haas N, Kluger HM. Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805. Clinical Cancer Research 2018, 24: 217-223. PMID: 29066509, PMCID: PMC5904512, DOI: 10.1158/1078-0432.ccr-17-1555.Peer-Reviewed Original ResearchConceptsHigher microvessel densityDisease-free survivalRenal cell carcinomaHigh-risk RCC patientsImproved overall survivalOverall survivalMicrovessel densityRCC patientsAdjuvant therapy trialsClear cell histologyHigh-risk patientsBiomarkers of outcomeTumor microvessel densityLower microvessel densityAbsence of necrosisFuhrman grade 1Clin Cancer ResAdjuvant sunitinibProlonged OSCell histologyLymphovascular invasionSarcomatoid featuresMultivariable analysisTreatment armsEntire cohort
2017
PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors
Kluger HM, Zito CR, Turcu G, Baine M, Zhang H, Adeniran A, Sznol M, Rimm DL, Kluger Y, Chen L, Cohen JV, Jilaveanu LB. PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors. Clinical Cancer Research 2017, 23: 4270-4279. PMID: 28223273, PMCID: PMC5540774, DOI: 10.1158/1078-0432.ccr-16-3146.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-L1 expressionRenal cell carcinomaPD-1 inhibitorsCell carcinomaImmune-infiltrating cellsMelanoma patientsPD-L1Tumor cellsTumor typesTumor-associated inflammatory cellsCTLA-4 inhibitorsCell lung cancerRenal cell carcinoma cellsHigh response rateClin Cancer ResCell linesMelanoma tumor cellsPD-1Multivariable analysisNSCLC specimensInflammatory cellsLung cancerTissue microarrayResponse rate
2016
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohortMelanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment
Cohen JV, Alomari AK, Vortmeyer AO, Jilaveanu LB, Goldberg SB, Mahajan A, Chiang VL, Kluger HM. Melanoma Brain Metastasis Pseudoprogression after Pembrolizumab Treatment. Cancer Immunology Research 2016, 4: 179-182. PMID: 26701266, PMCID: PMC4881844, DOI: 10.1158/2326-6066.cir-15-0160.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBrain NeoplasmsDisease ProgressionFemaleHumansMelanomaMiddle AgedSkin NeoplasmsConceptsCentral nervous systemBrain metastasesActive brain lesionsNew immunomodulating agentsImmune checkpoint inhibitorsRole of immunotherapyPembrolizumab treatmentCheckpoint inhibitorsCNS lesionsReactive astrocytosisImmune suppressionPerilesional edemaInflammatory cellsMicroglial cellsImmunomodulating agentMental statusBrain lesionsHistologic evaluationMost trialsNervous systemCentral enhancementTumor cellsPatientsMetastasisLesions
2013
Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel
Jilaveanu LB, Zhao F, Zito CR, Kirkwood JM, Nathanson KL, D'Andrea K, Wilson M, Rimm DL, Flaherty KT, Lee SJ, Kluger HM. Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel. PLOS ONE 2013, 8: e69748. PMID: 23936348, PMCID: PMC3735539, DOI: 10.1371/journal.pone.0069748.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalVEGF-R1FGF-R1Paclitaxel-based therapyVEGF-R1 expressionPre-treatment tumorsPredictive biomarker signaturesMultitarget kinase inhibitorPDGF-RβSitu protein expressionTherapeutic ratioTaxane sensitivityMitogen-activated protein kinase pathwayPatientsVEGF-R3CarboplatinSorafenibVEGF-R2C-kitKinase inhibitorsTherapyProtein expressionPhase IIISorafenib targetsAdvances in therapy for melanoma brain metastases
Flanigan JC, Jilaveanu LB, Chiang VL, Kluger HM. Advances in therapy for melanoma brain metastases. Clinics In Dermatology 2013, 31: 264-281. PMID: 23608446, DOI: 10.1016/j.clindermatol.2012.08.008.Peer-Reviewed Original ResearchStudies of NVP-BEZ235 in melanoma.
Sznol JA, Jilaveanu LB, Kluger HM. Studies of NVP-BEZ235 in melanoma. Current Cancer Drug Targets 2013, 13: 165-74. PMID: 23215722, DOI: 10.2174/1568009611313020006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsClinical Trials as TopicHumansImidazolesMelanomaPhosphoinositide-3 Kinase InhibitorsQuinolinesTOR Serine-Threonine KinasesConceptsNVP-BEZ235Dual PI3K/mTOR inhibitorNovel dual PI3K/mTOR inhibitorPI3K/mTOR inhibitorSpecific molecular inhibitorsPotential escape mechanismsMTOR inhibitorsPI3K-pathwayEscape mechanismsMulti-level targetingMalignant melanocytesMolecular inhibitorsDrug developmentMelanomaAttractive targetInhibitorsPathwayNumerous studies
2012
Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells
Zito CR, Jilaveanu LB, Anagnostou V, Rimm D, Bepler G, Maira SM, Hackl W, Camp R, Kluger HM, Chao HH. Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells. PLOS ONE 2012, 7: e31331. PMID: 22355357, PMCID: PMC3280285, DOI: 10.1371/journal.pone.0031331.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic AgentsBlotting, WesternCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCell Line, TumorCell ProliferationClass Ia Phosphatidylinositol 3-KinaseDrug SynergismFemaleFluorescent Antibody TechniqueHumansImmunoenzyme TechniquesLung NeoplasmsMaleMiddle AgedPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSignal TransductionTissue Array AnalysisTOR Serine-Threonine KinasesConceptsNon-small cell lung cancerNSCLC cell linesDual PI3K/mTOR inhibitorPI3K/AKT/mTOR pathwayPI3K/mTOR inhibitorAKT/mTOR pathwayPI3K inhibitorsNVP-BEZ235MTOR inhibitorsNVP-BKM120MTOR expressionAdvanced stageCell linesMTOR pathwayPI3K subunitsNon-small cell lung cancer cellsK inhibitorsCell lung cancer cellsCell lung cancerSquamous cell carcinomaP85 expressionSynergistic growth inhibitionRegulation of pAktExpression of p85Lung cancer cells
2010
A phase 2 trial of dasatinib in advanced melanoma
Kluger HM, Dudek AZ, McCann C, Ritacco J, Southard N, Jilaveanu LB, Molinaro A, Sznol M. A phase 2 trial of dasatinib in advanced melanoma. Cancer 2010, 117: 2202-2208. PMID: 21523734, PMCID: PMC3116034, DOI: 10.1002/cncr.25766.Peer-Reviewed Original ResearchConceptsProgression-free survivalC-kit mutationsPhase 2 trialResponse ratePartial responseMedian progression-free survivalMelanoma cell proliferationDaily dasatinibMucosal primaryPFS ratesStarting dosageCommon toxicitiesUnresectable melanomaAdvanced melanomaPleural effusionMelanoma patientsPredictive biomarkersMinor responseCombination trialsTumor assessmentDose reductionPatientsPrespecified endpointsDasatinibMelanoma