2024
Patterns of brain metastases response to immunotherapy with pembrolizumab
Mahajan A, Goldberg S, Weiss S, Tran T, Singh K, Joshi K, Aboian M, Kluger H, Chiang V. Patterns of brain metastases response to immunotherapy with pembrolizumab. Journal Of Neuro-Oncology 2024, 169: 555-561. PMID: 38963658, DOI: 10.1007/s11060-024-04754-8.Peer-Reviewed Original ResearchNon-small cell lung cancerBrain metastasesComplete resolutionLung cancerMedian time to CNS progressionLesion progressionNon-small cell lung cancer patientsModified RECIST criteriaPD-1 inhibitorsTrial of pembrolizumabEffective systemic treatmentResponse to immunotherapyPhase II trialCell lung cancerMethodsThis retrospective studyLocal treatment decisionsPurposeCentral nervous systemCNS progressionRECIST criteriaPD-1Local therapySystemic treatmentMRI evaluationResponse assessmentRetrospective studyImmunotherapy Initiation at the End of Life in Patients With Metastatic Cancer in the US
Kerekes D, Frey A, Prsic E, Tran T, Clune J, Sznol M, Kluger H, Forman H, Becher R, Olino K, Khan S. Immunotherapy Initiation at the End of Life in Patients With Metastatic Cancer in the US. JAMA Oncology 2024, 10: 342-351. PMID: 38175659, PMCID: PMC10767643, DOI: 10.1001/jamaoncol.2023.6025.Peer-Reviewed Original ResearchNon-small cell lung cancerEnd of lifeMonth of deathImmunotherapy initiationCohort studyMAIN OUTCOMEStage IV non-small cell lung cancerCharlson-Deyo comorbidity indexHigh metastatic burdenInitiation of immunotherapyNational prescribing patternsRisk-adjusted patientsImmune checkpoint inhibitorsRetrospective cohort studyStage IV melanomaPercentage of patientsHigh-volume centersLocation of metastasesLow-volume centersOdds of deathCell lung cancerNational Clinical DatabaseLow-volume facilitiesDrug Administration approvalCheckpoint inhibitors
2022
Association Between Food and Drug Administration Approval and Disparities in Immunotherapy Use Among Patients With Cancer in the US
Ermer T, Canavan ME, Maduka RC, Li AX, Salazar MC, Kaminski MF, Pichert MD, Zhan PL, Mase V, Kluger H, Boffa DJ. Association Between Food and Drug Administration Approval and Disparities in Immunotherapy Use Among Patients With Cancer in the US. JAMA Network Open 2022, 5: e2219535. PMID: 35771575, PMCID: PMC9247736, DOI: 10.1001/jamanetworkopen.2022.19535.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerRenal cell carcinomaUse of immunotherapyFDA approvalImmunotherapy useCohort studyClinical trialsNovel therapiesStage IV non-small cell lung cancerMultivariable logistic regression modelingFirst checkpoint inhibitorCheckpoint inhibitor therapyNational Cancer DatabasePatients 20 yearsCell lung cancerSocioeconomic strataTreatment of patientsDrug Administration approvalLife-saving treatmentReceipt of immunotherapyLogistic regression modelingSocioeconomic characteristicsImmunotherapy administrationCheckpoint inhibitorsPatient characteristics
2021
A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1
Weiss SA, Djureinovic D, Jessel S, Krykbaeva I, Zhang L, Jilaveanu L, Ralabate A, Johnson B, Levit NS, Anderson G, Zelterman D, Wei W, Mahajan A, Trifan O, Bosenberg M, Kaech SM, Perry CJ, Damsky W, Gettinger S, Sznol M, Hurwitz M, Kluger HM. A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1. Clinical Cancer Research 2021, 27: 4757-4767. PMID: 34140403, PMCID: PMC9236708, DOI: 10.1158/1078-0432.ccr-21-0903.Peer-Reviewed Original ResearchConceptsAnti-PD-1/PD-L1Non-small cell lung cancerCell lung cancerRenal cell carcinomaPD-L1Lung cancerDisease progressionCommon treatment-related adverse eventsPD-1/PD-L1 inhibitorsTreatment-related adverse eventsPhase 2 doseSubstantial clinical challengeUnconfirmed partial responseDose-limiting toxicityPD-L1 inhibitorsPhase I trialDose-escalation designPro-inflammatory cytokinesMultiple tumor typesAsymptomatic elevationStable diseaseIntolerable toxicityAdverse eventsMedian durationPartial responseProlonged Complete Response of Early Stage Primary Adenocarcinoma of the Lung to Nivolumab Monotherapy.
Unlu S, Grant MJ, Gettinger S, Adeniran A, Kluger HM. Prolonged Complete Response of Early Stage Primary Adenocarcinoma of the Lung to Nivolumab Monotherapy. Clinical Oncology Case Reports 2021, 4 PMID: 34382032, PMCID: PMC8353529.Peer-Reviewed Original ResearchMultiple primary malignant tumorsNivolumab monotherapyCheckpoint inhibitorsLung cancerHigh Programmed-Death Ligand 1 (PD-L1) expressionProgrammed Death Ligand 1 ExpressionNon-small cell lung cancerMultiple regional lymph nodesImmune checkpoint inhibitorsPD-1 inhibitorsLigand 1 expressionPrimary lung cancerEarly-stage diseaseRegional lymph nodesCell lung cancerPrimary malignant tumorsHigh-risk natureSystemic immunotherapyDurable responsesAdvanced melanomaComplete responseEffective immunotherapyLymph nodesMore patientsPrimary adenocarcinoma
2020
PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice
Eguren-Santamaria I, Sanmamed MF, Goldberg SB, Kluger HM, Idoate MA, Lu B, Corral J, Schalper KA, Herbst RS, Gil-Bazo I. PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice. Clinical Cancer Research 2020, 26: 4186-4197. PMID: 32354698, DOI: 10.1158/1078-0432.ccr-20-0798.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsAnti-PD-1/PD-L1 antibodiesAdvanced non-small cell lung cancerNSCLC brain metastasesBrain metastasesPD-L1 antibodiesAnti-PD-1/PD-L1 agentsPD-1/PD-L1 blockersActive central nervous system (CNS) involvementHigh PD-L1 expressionAnti-PD-1/PD-L1 drugsCentral nervous system involvementPivotal phase III trialsActive brain metastasesCNS response ratesPD-L1 agentsPD-L1 blockersSystemic therapy combinationsNervous system involvementPD-L1 expressionPhase III trialsSubset of patientsCell lung cancerPD-L1 drugs
2019
High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling
Toki MI, Merritt CR, Wong PF, Smithy JW, Kluger HM, Syrigos KN, Ong GT, Warren SE, Beechem JM, Rimm DL. High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling. Clinical Cancer Research 2019, 25: 5503-5512. PMID: 31189645, PMCID: PMC6744974, DOI: 10.1158/1078-0432.ccr-19-0104.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryImmunotherapyLymphocytes, Tumor-InfiltratingMaleMelanomaMolecular Diagnostic TechniquesMolecular Targeted TherapyPrognosisProportional Hazards ModelsTissue Array AnalysisTreatment OutcomeConceptsNon-small cell lung cancerProlonged progression-free survivalDigital spatial profilingOverall survivalPD-L1Predictive markerPD-L1 expressionProgression-free survivalProtein expressionCell lung cancerNovel predictive markerCD68-positive cellsStromal CD3Melanoma immunotherapyImmune markersImmune therapyPrognostic valueLung cancerAntibody cocktailTissue microarrayQuantitative fluorescenceOutcome assessmentTumor cellsHigh concordanceMultiple biomarkers
2018
Final Results of a Phase I Prospective Trial Evaluating the Combination of Stereotactic Body Radiation Therapy (SBRT) with Concurrent Pembrolizumab in Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC) or Melanoma
Campbell A, Herbst R, Gettinger S, Goldberg S, Kluger H, Chiang A, Lilenbaum R, Schalper K, Sowell R, Kaech S, Decker R. Final Results of a Phase I Prospective Trial Evaluating the Combination of Stereotactic Body Radiation Therapy (SBRT) with Concurrent Pembrolizumab in Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC) or Melanoma. International Journal Of Radiation Oncology • Biology • Physics 2018, 102: s18-s19. DOI: 10.1016/j.ijrobp.2018.06.134.Peer-Reviewed Original ResearchDurability of brain metastasis response and overall survival in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab.
Goldberg S, Gettinger S, Mahajan A, Herbst R, Chiang A, Lilenbaum R, Jilaveanu L, Rowen E, Gerrish H, Komlo A, Wei W, Chiang V, Kluger H. Durability of brain metastasis response and overall survival in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab. Journal Of Clinical Oncology 2018, 36: 2009-2009. DOI: 10.1200/jco.2018.36.15_suppl.2009.Peer-Reviewed Original ResearchFinal results of a phase I prospective trial evaluating the combination of stereotactic body radiotherapy (SBRT) with concurrent pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC) or melanoma.
Campbell A, Herbst R, Gettinger S, Goldberg S, Kluger H, Chiang A, Lilenbaum R, Schalper K, Sowell R, Kaech S, Decker R. Final results of a phase I prospective trial evaluating the combination of stereotactic body radiotherapy (SBRT) with concurrent pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC) or melanoma. Journal Of Clinical Oncology 2018, 36: 9099-9099. DOI: 10.1200/jco.2018.36.15_suppl.9099.Peer-Reviewed Original ResearchSafety and feasibility of immuno-cryotherapy.
Raja J, Ghodadra A, Gettinger S, Kluger H, Sznol M, Schalper K, "Kevin" Kim H. Safety and feasibility of immuno-cryotherapy. Journal Of Clinical Oncology 2018, 36: 34-34. DOI: 10.1200/jco.2018.36.5_suppl.34.Peer-Reviewed Original ResearchAdverse eventsImage-guided cryotherapyGrade 3Metastatic non-small cell lung cancerNon-small cell lung cancerImmune checkpoint inhibitor resistanceImmune checkpoint inhibitor therapyAdverse Events criteriaCheckpoint inhibitor resistanceCheckpoint inhibitor therapyCTLA-4 blockadeDisease control rateHigher adverse eventsImmune checkpoint inhibitionPrimary end pointImmune checkpoint therapyCell lung cancerTypes of malignanciesCases of diarrheaProgression of diseaseSystemic immunotherapyMetastatic NSCLCPeriprocedural periodSecondary endpointsSite hematoma
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 cohort
2015
Activity and safety of pembrolizumab in patients with metastatic non-small cell lung cancer with untreated brain metastases.
Goldberg S, Gettinger S, Mahajan A, Herbst R, Chiang A, Tsiouris A, Vortmeyer A, Jilaveanu L, Speaker S, Madura M, Rowen E, Gerrish H, Knapp-Perry E, Yao X, Chiang V, Kluger H. Activity and safety of pembrolizumab in patients with metastatic non-small cell lung cancer with untreated brain metastases. Journal Of Clinical Oncology 2015, 33: 8035-8035. DOI: 10.1200/jco.2015.33.15_suppl.8035.Peer-Reviewed Original Research
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