2021
Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760)
Leighl NB, Redman MW, Rizvi N, Hirsch FR, Mack PC, Schwartz LH, Wade JL, Irvin WJ, Reddy SC, Crawford J, Bradley JD, Stinchcombe TE, Ramalingam SS, Miao J, Minichiello K, Herbst RS, Papadimitrakopoulou VA, Kelly K, Gandara DR. Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760). Journal For ImmunoTherapy Of Cancer 2021, 9: e002973. PMID: 34429332, PMCID: PMC8386207, DOI: 10.1136/jitc-2021-002973.Peer-Reviewed Original ResearchConceptsDisease progressionAnti-programmed death ligand 1 therapyStage IV squamous cell lung cancerPrior anti-PD-1 therapyResponse rateAnti-PD-1 therapyDeath ligand 1 therapyMedian progression-free survivalSquamous cell lung cancerObjective response ratePhase II studyProgression-free survivalCell lung cancerSquamous lung carcinomaDurvalumab 1500Eligible patientsImmunotherapy combinationsPrimary endpointAdverse eventsII studyOverall survivalPartial responseTRIAL REGISTRATIONLung cancerLung carcinoma
2020
Chemoradiotherapy efficacy is predicted by intra-tumour CD8+/FoxP3+ double positive T cell density in locally advanced N2 non–small-cell lung carcinoma
Boulle G, Velut Y, Mansuet-Lupo A, Gibault L, Blons H, Fournel L, Boni A, Cremer I, Wislez M, Duchatelle V, Trédaniel J, Hammond S, Herbst R, Alifano M, Giraud P, Damotte D. Chemoradiotherapy efficacy is predicted by intra-tumour CD8+/FoxP3+ double positive T cell density in locally advanced N2 non–small-cell lung carcinoma. European Journal Of Cancer 2020, 135: 221-229. PMID: 32610210, DOI: 10.1016/j.ejca.2020.04.040.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overB7-H1 AntigenCarcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesChemoradiotherapyChemoradiotherapy, AdjuvantFemaleForkhead Transcription FactorsHumansLung NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm StagingRetrospective StudiesTime FactorsTreatment OutcomeTumor MicroenvironmentConceptsT-cell densityCell lung carcinomaN2 NSCLCPatient survivalLung carcinomaClinical dataT cellsRadiotherapy efficacyIII-N2 NSCLCSurgery/chemotherapyPD-L1 expressionStandard of careImmunogenic cell deathDouble-positive cellsAction of radiotherapyIII-N2Immune environmentAbscopal effectChemoradiotherapy efficacyImmune infiltrationImmune cellsPositive cellsMultivariate analysisRadiotherapyTumor samplesSWOG S1400F (NCT03373760): A phase II study of durvalumab plus tremelimumab for previously treated patients with acquired resistance to PD-1 checkpoint inhibitor therapy and stage IV squamous cell lung cancer (Lung-MAP Sub-study).
Leighl N, Redman M, Rizvi N, Hirsch F, Mack P, Schwartz L, Wade J, Irvin W, Reddy S, Crawford J, Bradley J, Stinchcombe T, Ramalingam S, Miao J, Minichiello K, Gandara D, Herbst R, Papadimitrakopoulou V, Kelly K. SWOG S1400F (NCT03373760): A phase II study of durvalumab plus tremelimumab for previously treated patients with acquired resistance to PD-1 checkpoint inhibitor therapy and stage IV squamous cell lung cancer (Lung-MAP Sub-study). Journal Of Clinical Oncology 2020, 38: 9623-9623. DOI: 10.1200/jco.2020.38.15_suppl.9623.Peer-Reviewed Original ResearchSquamous lung carcinomaLung carcinomaMedian PFSAdverse eventsObjective responseDisease progressionStage IV squamous cell lung cancerPD-1 checkpoint inhibitor therapySquamous cell lung cancerPD-1 checkpoint inhibitorsGood responseAdequate organ functionGrade 4 dyspneaPerformance status 0PR/SDTreatment-related deathsCheckpoint inhibitor therapyImmune-related toxicitiesPhase II studyPD-1 inhibitionBest objective responseCell lung cancerEligible patientsQ28 daysStatus 0
2018
A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers
Gettinger SN, Choi J, Mani N, Sanmamed MF, Datar I, Sowell R, Du VY, Kaftan E, Goldberg S, Dong W, Zelterman D, Politi K, Kavathas P, Kaech S, Yu X, Zhao H, Schlessinger J, Lifton R, Rimm DL, Chen L, Herbst RS, Schalper KA. A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers. Nature Communications 2018, 9: 3196. PMID: 30097571, PMCID: PMC6086912, DOI: 10.1038/s41467-018-05032-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BlockingCarcinogenesisCarcinoma, Non-Small-Cell LungCell ProliferationCytotoxicity, ImmunologicHistocompatibility Antigens Class IHumansLung NeoplasmsLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleMice, Inbred NODMice, SCIDMutant ProteinsMutationPeptidesPhenotypeProgrammed Cell Death 1 ReceptorReproducibility of ResultsSurvival AnalysisTobaccoConceptsImmune checkpoint blockersCheckpoint blockersQuantitative immunofluorescenceNon-small cell lung carcinoma patientsCell lung carcinoma patientsNon-small cell lung carcinomaPatient-derived xenograft modelsIntratumoral T cellsMultiplexed quantitative immunofluorescencePD-1 blockadeLevels of CD3Lung carcinoma patientsCell lung carcinomaT cell proliferationPre-treatment samplesTIL phenotypeSurvival benefitCarcinoma patientsEffector capacityLung carcinomaT cellsWhole-exome DNA sequencingXenograft modelFavorable responseBlockersMultiplexed analysis of myeloid cell (MC) markers to characterize the innate immune composition and clinical features of human non-small cell lung carcinomas (NSCLC).
Henick B, Datar I, Villarroel-Espindola F, Sanmamed M, Yu J, Tuktamyshov R, Li A, Toki M, Syrigos K, Rimm D, Chen L, Herbst R, Schalper K. Multiplexed analysis of myeloid cell (MC) markers to characterize the innate immune composition and clinical features of human non-small cell lung carcinomas (NSCLC). Journal Of Clinical Oncology 2018, 36: 12002-12002. DOI: 10.1200/jco.2018.36.15_suppl.12002.Peer-Reviewed Original ResearchClinical and Molecular Characteristics Associated With Survival Among Patients Treated With Checkpoint Inhibitors for Advanced Non–Small Cell Lung Carcinoma: A Systematic Review and Meta-analysis
Lee CK, Man J, Lord S, Cooper W, Links M, Gebski V, Herbst RS, Gralla RJ, Mok T, Yang JC. Clinical and Molecular Characteristics Associated With Survival Among Patients Treated With Checkpoint Inhibitors for Advanced Non–Small Cell Lung Carcinoma: A Systematic Review and Meta-analysis. JAMA Oncology 2018, 4: 210-216. PMID: 29270615, PMCID: PMC5838598, DOI: 10.1001/jamaoncol.2017.4427.Peer-Reviewed Original ResearchConceptsNon-small cell lung carcinomaAdvanced non-small cell lung carcinomaSecond-line therapyCheckpoint inhibitorsOverall survivalCell lung carcinomaWild-type subgroupClinicopathological characteristicsHazard ratioClinical trialsLung carcinomaMutant subgroupSystematic reviewKRAS wild-type subgroupStandard second-line therapyKRAS mutant subgroupRelative treatment benefitOverall survival benefitCochrane Central RegisterType of chemotherapyProlonged overall survivalProlongs overall survivalEGFR-mutant tumorsPatients' clinicopathological characteristicsRandomized clinical trials
2017
Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers.
Datar I, Mani N, Henick B, Wurtz A, Kaftan E, Herbst R, Rimm D, Gettinger S, Politi K, Schalper K. Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers. Journal Of Clinical Oncology 2017, 35: e14611-e14611. DOI: 10.1200/jco.2017.35.15_suppl.e14611.Peer-Reviewed Original ResearchNon-small cell lung carcinomaTim-3PD-1LAG-3T cellsInhibitory receptorsAdvanced non-small cell lung carcinomaPD-1 axis blockadeHigh TIM-3Immune suppressive pathwaysImmune inhibitory receptorsCell lung carcinomaMembranous staining patternPre-treatment samplesWhole tissue sectionsWhole tumor areaClinical responseMost patientsAxis blockadeLow levelsLung carcinomaT lymphocytesMultiplex immunofluorescenceHigh levelsSuppressive pathwaysDifferential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer
Schalper KA, Carvajal-Hausdorf D, McLaughlin J, Altan M, Velcheti V, Gaule P, Sanmamed MF, Chen L, Herbst RS, Rimm DL. Differential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer. Clinical Cancer Research 2017, 23: 370-378. PMID: 27440266, PMCID: PMC6350535, DOI: 10.1158/1078-0432.ccr-16-0150.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAgedB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungDisease-Free SurvivalDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaInterleukin-10Lymphocytes, Tumor-InfiltratingMiddle AgedNeoplasm StagingRNA, MessengerV-Set Domain-Containing T-Cell Activation Inhibitor 1ConceptsNon-small cell lung cancerB7-H4PD-L1IDO-1Lung cancerLung carcinomaQuantitative immunofluorescenceIFNγ stimulationElevated PD-L1Major clinicopathologic variablesMultiplexed quantitative immunofluorescenceOptimal clinical trialsT-cell infiltratesCell lung cancerImmune evasion pathwaysHuman lung carcinomaLung adenocarcinoma A549Cancer Genome AtlasClinicopathologic variablesMarker levelsClinical trialsStage ITherapeutic resistanceTCGA datasetA549 cells
2011
Increased VEGFR-2 Gene Copy Is Associated with Chemoresistance and Shorter Survival in Patients with Non–Small-Cell Lung Carcinoma Who Receive Adjuvant Chemotherapy
Yang F, Tang X, Riquelme E, Behrens C, Nilsson MB, Giri U, Varella-Garcia M, Byers LA, Lin HY, Wang J, Raso MG, Girard L, Coombes K, Lee JJ, Herbst RS, Minna JD, Heymach JV, Wistuba II. Increased VEGFR-2 Gene Copy Is Associated with Chemoresistance and Shorter Survival in Patients with Non–Small-Cell Lung Carcinoma Who Receive Adjuvant Chemotherapy. Cancer Research 2011, 71: 5512-5521. PMID: 21724587, PMCID: PMC3159530, DOI: 10.1158/0008-5472.can-10-2614.Peer-Reviewed Original ResearchConceptsCell lung carcinomaHIF-1α levelsAdjuvant therapyLung carcinomaAdjuvant platinum-based chemotherapyVEGFR-2 blockadeNuclear hypoxia inducible factor-1αNSCLC tumor cellsPlatinum-based chemotherapyFavorable overall survivalRisk of deathHypoxia-inducible factor-1αHigher microvessel densityNSCLC tumor specimensNSCLC cell linesInducible factor-1αCell linesVEGF receptor 2Adjuvant chemotherapyOverall survivalClinical outcomesAdenocarcinoma patientsMicrovessel densityShorter SurvivalHigh risk
2004
Potential role of molecularly targeted therapy in the management of advanced nonsmall cell lung carcinoma in the elderly
Gridelli C, Massarelli E, Maione P, Rossi A, Herbst RS, Onn A, Ciardiello F. Potential role of molecularly targeted therapy in the management of advanced nonsmall cell lung carcinoma in the elderly. Cancer 2004, 101: 1733-1744. PMID: 15386339, DOI: 10.1002/cncr.20572.Peer-Reviewed Original ResearchConceptsAdvanced nonsmall cell lung carcinomaNonsmall cell lung carcinomaNovel biologic agentsElderly patientsCell lung carcinomaConventional chemotherapyPatient ageBiologic agentsLung carcinomaClinical developmentSuch elderly patientsVascular endothelial growth factorLung carcinoma casesQuality of lifeEndothelial growth factorEpidermal growth factor receptorGrowth factor receptorAggressive chemotherapyImproved tolerabilityYounger patientsOrgan failureTherapy regimensComorbid conditionsMalignant diseaseCarcinoma cases
2002
The novel and effective nonplatinum, nontaxane combination of gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma
Herbst RS, Khuri FR, Lu C, Liu DD, Fossella FV, Glisson BS, Pisters KM, Shin DM, Papadimitrakopoulou VA, Kurie JM, Blumenschein G, Kies MS, Zinner R, Jung MS, Lu R, Lee JJ, Munden RF, Hong WK, Lee JS. The novel and effective nonplatinum, nontaxane combination of gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma. Cancer 2002, 95: 340-353. PMID: 12124835, DOI: 10.1002/cncr.10629.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntimetabolites, AntineoplasticAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsBiological TherapyCarcinoma, Non-Small-Cell LungCombined Modality TherapyDeoxycytidineDisease ProgressionFemaleGemcitabineHumansLung NeoplasmsMaleMiddle AgedSurvival RateVinblastineVinorelbineConceptsNonsmall cell lung carcinomaYear survival rateAdvanced nonsmall cell lung carcinomaThird-line therapyPhase II trialMedian survival timeCell lung carcinomaGrade 3Survival rateSignificant myelosuppressionStable diseaseII trialLung carcinomaSurvival timeStage IV nonsmall cell lung carcinomaDay 1Day 15Formal phase II trialCurrent phase II trialDose of vinorelbineGemcitabine/vinorelbineGrade 3 granulocytopeniaMedian performance statusMinimal grade 3Prior chemotherapy regimens
2000
Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage I non-small cell lung carcinoma.
Herbst RS, Yano S, Kuniyasu H, Khuri FR, Bucana CD, Guo F, Liu D, Kemp B, Lee JJ, Hong WK, Fidler IJ. Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage I non-small cell lung carcinoma. Clinical Cancer Research 2000, 6: 790-7. PMID: 10741698.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCadherinsCarcinoma, Non-Small-Cell LungDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansIn Situ HybridizationLung NeoplasmsMaleMatrix Metalloproteinase 2Matrix Metalloproteinase 9Middle AgedMultivariate AnalysisNeoplasm MetastasisNeoplasm Recurrence, LocalNeoplasm StagingPredictive Value of TestsSurvival AnalysisConceptsE-cadherin ratioLung cancerType IV collagenaseLung carcinomaDisease outcomeStage I non-small cell lung carcinomaPrimary non-small cell lung cancerNon-small cell lung cancerE-cadherinKaplan-Meier survival analysisNon-small cell lung carcinomaD. Anderson Cancer CenterResectable lung cancerDisease-free survivalSignificant prognostic factorsLonger overall survivalCell lung cancerDisease recurrence rateRoutine histopathological examinationCox univariate analysisAnderson Cancer CenterCell lung carcinomaVascular endothelial growth factor/vascular permeability factorHuman lung cancerBasic fibroblast growth factor
1999
The proteasome inhibitor PS-341 in cancer therapy.
Teicher B, Ara G, Herbst R, Palombella V, Adams J. The proteasome inhibitor PS-341 in cancer therapy. Clinical Cancer Research 1999, 5: 2638-45. PMID: 10499643.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBoronic AcidsBortezomibBreast NeoplasmsCisplatinCyclophosphamideDipeptidesDrug SynergismHumansMammary Neoplasms, ExperimentalMiceMice, Inbred BALB CProtease InhibitorsPyrazinesRadiation-Sensitizing AgentsTumor Cells, CulturedUbiquitinsConceptsProteasome inhibitor PS-341PS-341EMT-6/CDDP tumorAdditive tumor growth delayCancer therapyEMT-6/CTXTumor cell survival assayTumor growth delay assayLewis lung carcinomaColony-forming unit-granulocyte macrophageTumor growth delayGrowth delay assayHuman breast carcinoma cellsMCF-7 human breast carcinoma cellsUnit-granulocyte macrophageTumor cell killingCell survival assayBreast carcinoma cellsMetastatic diseaseInteresting new targetLung carcinomaRadiation therapyVivo resistanceGrowth delayParent tumor
1998
Paclitaxel/carboplatin administration along with antiangiogenic therapy in non-small-cell lung and breast carcinoma models
Herbst R, Takeuchi H, Teicher B. Paclitaxel/carboplatin administration along with antiangiogenic therapy in non-small-cell lung and breast carcinoma models. Cancer Chemotherapy And Pharmacology 1998, 41: 497-504. PMID: 9554595, DOI: 10.1007/s002800050773.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBone Marrow CellsCarboplatinCarcinoma, Lewis LungCell SurvivalColony-Forming Units AssayCyclohexanesDrug SynergismDrug Therapy, CombinationFemaleMaleMammary Neoplasms, ExperimentalMiceMice, Inbred BALB CMice, Inbred C57BLMinocyclineNeovascularization, PathologicO-(Chloroacetylcarbamoyl)fumagillolPaclitaxelSesquiterpenesConceptsTNP-470/minocyclineEMT-6 mammary carcinomaBone marrow CFU-GMLewis lung carcinomaMarrow CFU-GMEMT-6 tumor cellsLung carcinomaMammary carcinomaCFU-GMNormal tissuesTumor cellsHigh-dose paclitaxelCell lung cancerCombination of paclitaxelToxicity of carboplatinEfficacy of chemotherapyTumor growth delayBreast carcinoma modelCytotoxicity of carboplatinEarly time pointsAgent regimenAntiangiogenic regimenCarboplatin administrationLung metastasesCell lungPotential of the aminosterol, squalamine in combination therapy in the rat 13,762 mammary carcinoma and the murine Lewis lung carcinoma.
Teicher BA, Williams JI, Takeuchi H, Ara G, Herbst RS, Buxton D. Potential of the aminosterol, squalamine in combination therapy in the rat 13,762 mammary carcinoma and the murine Lewis lung carcinoma. Anticancer Research 1998, 18: 2567-73. PMID: 9703911.Peer-Reviewed Original ResearchMeSH Keywords9,10-Dimethyl-1,2-benzanthraceneAnimalsAnticarcinogenic AgentsAntineoplastic AgentsCarcinoma, Lewis LungCell DivisionCholestanolsCisplatinCombined Modality TherapyCyclophosphamideDoxorubicinDrug Therapy, CombinationFemaleFluorouracilMammary Neoplasms, ExperimentalMiceOxygenOxygen ConsumptionPaclitaxelPartial PressureRatsRats, Inbred F344ConceptsLewis lung carcinomaTumor growth delayPost-tumor implantationLung carcinomaGrowth delayLung metastasesTumor implantationMammary carcinomaTumor oxygenationDay 4Chemotherapeutic agentsPrimary Lewis lung tumorMurine Lewis lung carcinomaDaily subcutaneous injectionsLewis lung tumorTumor-bearing animalsModest effectCombination therapyContinuous infusionCytotoxic therapySystemic diseaseSubcutaneous injectionLung tumorsAntiangiogenic agentsHypoxic fraction