2024
SWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer.
Reckamp K, Redman M, Dragnev K, Iams W, Henick B, Miao J, LeBlanc M, Carrizosa D, Herbst R, Blanke C, Gray J. SWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer. Journal Of Clinical Oncology 2024, 42: tps8657-tps8657. DOI: 10.1200/jco.2024.42.16_suppl.tps8657.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerStandard of careCell lung cancerPD-(L)1Overall survivalAdverse eventsRecurrent non-small cell lung cancerLung cancerTreatment-related adverse eventsRandomized phase II trialStandard of care treatmentPlatinum-based therapyTreated with immunotherapyPhase II trialLog-rank testCompare OSInhibitor therapyII trialCombination therapyStatistically significant improvementTumor resistanceSafety profileTherapeutic optionsRandomized study
2023
Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results
Gutierrez M, Lam W, Hellmann M, Gubens M, Aggarwal C, Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Finocchiaro G, Ahn M, Luft A, Landers G, Basso A, Ma H, Kobie J, Palcza J, Cristescu R, Fong L, Snyder A, Yuan J, Herbst R. Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Nature Medicine 2023, 29: 1718-1727. PMID: 37429923, DOI: 10.1038/s41591-023-02385-6.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerObjective response rateAdvanced non-small cell lung cancerCell lung cancerSafety profileCombination therapyLung cancerInvestigator-assessed objective response rateRandomized phase 2 studySolid Tumors version 1.1T-cell-inflamed gene expression profileGroup IIIBiomarker-defined subgroupsFirst-line pembrolizumabPhase 2 studyProgression-free survivalResponse Evaluation CriteriaSubset of patientsHeterogenous tumor microenvironmentData cutoffOverall survivalSecondary outcomesPrimary outcomeTreatment armsTMB assessment
2022
635 KEYNOTE-495/KeyImPaCT: updated analysis of a biomarker-directed, randomized, phase 2 trial of pembrolizumab-based combination therapy for non-small cell lung cancer
Herbst R, Lam W, Hellmann M, Gubens M, Aggarwal C, Weng Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Finocchiaro G, Ahn M, Luft A, Landers G, Basso A, Ma H, Kobie J, Palcza J, Cristescu R, Fong L, Snyder A, Yuan J, Gutierrez M. 635 KEYNOTE-495/KeyImPaCT: updated analysis of a biomarker-directed, randomized, phase 2 trial of pembrolizumab-based combination therapy for non-small cell lung cancer. 2022, a666-a666. DOI: 10.1136/jitc-2022-sitc2022.0635.Peer-Reviewed Original Research
2021
457 KEYNOTE-495/KeyImPaCT: interim analysis of a randomized, biomarker-directed, phase 2 trial of pembrolizumab-based combination therapy for non–small cell lung cancer (NSCLC)
Gutierrez M, Lam W, Hellmann M, Gubens M, Aggarwal C, Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Finocchiaro G, Ahn M, Luft A, Landers G, Basso A, Ma H, Kobie J, Palcza J, Cristescu R, Fong L, Snyder A, Yuan J, Herbst R. 457 KEYNOTE-495/KeyImPaCT: interim analysis of a randomized, biomarker-directed, phase 2 trial of pembrolizumab-based combination therapy for non–small cell lung cancer (NSCLC). Journal For ImmunoTherapy Of Cancer 2021, 9: a485-a485. DOI: 10.1136/jitc-2021-sitc2021.457.Peer-Reviewed Original ResearchTreatment-related adverse eventsNon-small cell lung cancerAdvanced non-small cell lung cancerCombination therapyInterim analysisBiomarker subgroupsMost treatment-related adverse eventsT-cell-inflamed gene expression profileHigh subgroupBiomarker-defined subgroupsPrimary end pointPhase 2 studyPhase 2 trialFirst-line pembrolizumabCell lung cancerFirst interim analysisSubsidiary of MerckInstitutional review boardRECIST v1.1Data cutoffAdverse eventsDohme Corp.Lung cancerMature dataStudy protocolToward personalized treatment approaches for non-small-cell lung cancer
Wang M, Herbst RS, Boshoff C. Toward personalized treatment approaches for non-small-cell lung cancer. Nature Medicine 2021, 27: 1345-1356. PMID: 34385702, DOI: 10.1038/s41591-021-01450-2.Peer-Reviewed Original ResearchConceptsCell lung cancerLung cancerCombination therapyMaintenance combination therapyRobust predictive biomarkersCancer-related deathPersonalized treatment approachesRational combination therapiesAdvanced NSCLCEarly diseasePredictive biomarkersClinical studiesCurrent treatmentCommon causePatient stratificationTreatment approachesTherapyNSCLCBreakthrough therapiesCancerClinical research areasImmunotherapyVast majorityCurrent understandingFuture role
2019
Biomarker-directed precision oncology of pembrolizumab-based combination therapy for non-small cell lung cancer: Phase II KEYNOTE-495/KeyImPaCT study.
Gutierrez M, Hellmann M, Gubens M, Aggarwal C, Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Basso A, Ma H, Fong L, Snyder A, Yuan J, Herbst R. Biomarker-directed precision oncology of pembrolizumab-based combination therapy for non-small cell lung cancer: Phase II KEYNOTE-495/KeyImPaCT study. Journal Of Clinical Oncology 2019, 37: tps9117-tps9117. DOI: 10.1200/jco.2019.37.15_suppl.tps9117.Peer-Reviewed Original ResearchCombination therapyRECIST v1.1Advanced NSCLCGene expression profilesInvestigator-assessed objective response rateNon-small cell lung cancerEnd pointT-cell-inflamed gene expression profileECOG PS 0Immune checkpoint inhibitorsObjective response ratePrimary end pointSecondary end pointsProgression-free survivalROS1 gene rearrangementCell lung cancerAbsence of EGFRInterim efficacy analysisDifferent combination therapiesCombination immunotherapyLenvatinib armLenvatinib monotherapyMeasurable diseaseCheckpoint inhibitorsPembrolizumab monotherapy
2018
The biology and management of non-small cell lung cancer
Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature 2018, 553: 446-454. PMID: 29364287, DOI: 10.1038/nature25183.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerSmall molecule tyrosine kinase inhibitorsMolecule tyrosine kinase inhibitorsBroader patient populationTyrosine kinase inhibitorsUnprecedented survival benefitsMetastatic diseaseMultimodal careSurvival benefitClinical benefitCombination therapyOverall curePatient populationSurvival rateTumor progressionEarly detectionKinase inhibitorsNew drugsDisease biologyCancerImmunotherapyPatientsTherapy
2017
Immuno-thermal ablations – boosting the anticancer immune response
Slovak R, Ludwig JM, Gettinger SN, Herbst RS, Kim HS. Immuno-thermal ablations – boosting the anticancer immune response. Journal For ImmunoTherapy Of Cancer 2017, 5: 78. PMID: 29037259, PMCID: PMC5644150, DOI: 10.1186/s40425-017-0284-8.Peer-Reviewed Original ResearchConceptsImmune responseImmune effectsRobust antitumor responseAnticancer immune responseImmune modulating drugsUse of immunomodulationSystemic antitumor activityCheckpoint blockadeAntitumor responseAblative therapyCombination therapyRadiofrequency ablationAblative techniquesModulating drugsAnimal modelsAntitumor activityThermal ablationTherapeutic appealImmunomodulationTherapyAblationResponseMonotherapyImmunomodulatorsCryoablation
2016
Nivolumab and Pembrolizumab for Non–Small Cell Lung Cancer
Morgensztern D, Herbst RS. Nivolumab and Pembrolizumab for Non–Small Cell Lung Cancer. Clinical Cancer Research 2016, 22: 3713-3717. PMID: 27252413, DOI: 10.1158/1078-0432.ccr-15-2998.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungClinical Trials, Phase I as TopicHumansLung NeoplasmsNivolumabPrognosisProgrammed Cell Death 1 ReceptorRandomized Controlled Trials as TopicTreatment OutcomeConceptsCheckpoint inhibitorsClinical trialsAdvanced stage non-small lung cancerDeath-1 checkpoint inhibitorsLarge randomized clinical trialsNon-small lung cancerSecond-line docetaxelSurvivors 3 yearsBest supportive careSubset of patientsRandomized clinical trialsOverall survivalSupportive careCombination therapyLung cancerModest benefitPatientsPhase IImmunotherapyReliable predictorTherapyInhibitorsTrialsTreatmentNivolumab
2012
The Microculture-Kinetic (MiCK) Assay: The Role of a Drug-Induced Apoptosis Assay in Drug Development and Clinical Care
Bosserman L, Prendergast F, Herbst R, Fleisher M, Salom E, Strickland S, Raptis A, Hallquist A, Perree M, Rajurkar S, Karimi M, Rogers K, Davidson D, Willis C, Penalver M, Homesley H, Burrell M, Garrett A, Rutledge J, Chernick M, Presant CA. The Microculture-Kinetic (MiCK) Assay: The Role of a Drug-Induced Apoptosis Assay in Drug Development and Clinical Care. Cancer Research 2012, 72: 3901-3905. PMID: 22865459, DOI: 10.1158/0008-5472.can-12-0681.Peer-Reviewed Original ResearchConceptsHigh response rateLonger survivalClinical trialsResponse rateGroup of patientsBlinded clinical trialEpithelial ovarian cancerApoptosis assaysAcute myelocytic leukemiaUnblinded clinical trialDrug developmentGeneric drug useMultiple tumor typesEfficient drug developmentCombination therapyOvarian cancerMyelocytic leukemiaClinical careTumor typesDrug useClinical therapyClinical useMolecular biomarkersDrug approvalHigher apoptosis
2010
Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo
Meng J, Dai B, Fang B, Bekele BN, Bornmann WG, Sun D, Peng Z, Herbst RS, Papadimitrakopoulou V, Minna JD, Peyton M, Roth JA. Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo. PLOS ONE 2010, 5: e14124. PMID: 21124782, PMCID: PMC2993951, DOI: 10.1371/journal.pone.0014124.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBenzimidazolesCarcinoma, Non-Small-Cell LungCell CycleCell Line, TumorCell SurvivalDose-Response Relationship, DrugDrug SynergismFemaleHeterocyclic Compounds, 3-RingHumansLung NeoplasmsMiceMice, Inbred BALB CMice, NudeMitogen-Activated Protein Kinase KinasesProto-Oncogene Proteins c-aktSignal TransductionSurvival AnalysisTumor BurdenXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerCell lung cancerCombination of AZD6244Lung cancer cell linesCombination therapyLung cancerCancer cell linesTumor growthTumor tissueHuman non-small cell lung cancerLung cancer cell growthCell linesHuman lung cancer cell linesSingle drug treatmentSynergistic antitumor activityHuman lung tumorsAnimal survival timeMean animal survival timeCancer cell growthXenograft tumor growthP-AKT expressionLung tumorsDrug treatmentDrug combinationsSurvival time
2003
The rationale and potential of combining novel biologic therapies with radiotherapy: focus on non-small cell lung cancer
Herbst RS, O’Reilly M. The rationale and potential of combining novel biologic therapies with radiotherapy: focus on non-small cell lung cancer. Seminars In Oncology 2003, 30: 113-123. PMID: 12908142, DOI: 10.1016/s0093-7754(03)00269-0.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerAnti-epidermal growth factor receptor agentsNovel biologic therapiesEarly clinical investigationConventional cytotoxic agentsNovel combination therapiesTreatment of malignanciesAnti-angiogenic agentsPresent preclinical dataBiologic therapyOngoing trialsCombination therapyPreclinical dataReceptor agentsToxicity profileClinical investigationClinical developmentConventional modalitiesCytotoxic agentsRadiotherapyTherapyCancerHuman cancers
2002
Targeted therapy in non-small-cell lung cancer.
Herbst RS. Targeted therapy in non-small-cell lung cancer. Oncology 2002, 16: 19-24. PMID: 12375797.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntibodies, MonoclonalAntineoplastic AgentsCarcinoma, Non-Small-Cell LungClinical Trials as TopicEndothelial Growth FactorsErbB ReceptorsHumansIntercellular Signaling Peptides and ProteinsLung NeoplasmsLymphokinesProtein Kinase CVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsCell lung cancerLung cancerSuch new agentsNew agentsVascular endothelial growth factor inhibitorsPlatinum-based combination therapyEGFR tyrosine kinase inhibitorsGrowth factor receptor inhibitorsNew biologic therapiesGrowth factor inhibitorsEpithelial growth factor receptor inhibitorTyrosine kinase inhibitorsSpecific biologic pathwaysDevelopment of agentsSignal transduction inhibitorsMaintenance therapyBiologic therapyCytotoxic chemotherapyStages of treatmentFactor inhibitorsCombination therapyTargeted therapyReceptor inhibitorsRadiation therapyClinical investigation
1998
Potential 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