2024
Precision needle-punch tumor enrichment from paraffin blocks improves the detection of clinically actionable genomic alterations and biomarkers
Lin D, Huang R, Ladas I, Keller R, Patel N, Lakis S, Decker B, Janovitz T, Mata D, Ross J, Vergilio J, Elvin J, Herbst R, Mack P, Killian J. Precision needle-punch tumor enrichment from paraffin blocks improves the detection of clinically actionable genomic alterations and biomarkers. Frontiers In Oncology 2024, 14: 1328512. PMID: 38444675, PMCID: PMC10912171, DOI: 10.3389/fonc.2024.1328512.Peer-Reviewed Original ResearchTumor mutational burdenTumor purityTumor specimensNext-generation sequencingClinically actionable genomic alterationsMicrosatellite instabilityBiomarker statusTissue-conserving methodTissue blocksHigh tumor purityLow tumor purityComplex biomarkersSurgical pathology materialClinical samplesClinical trial enrollmentVariant allele frequencyResidual tumorMutational burdenTumor enrichmentTumor contentTumor cellsGenomic alterationsFormalin-fixedParaffin blocksDetect mutations
2023
Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC ☆
Mok T, Lopes G, Cho B, Kowalski D, Kasahara K, Wu Y, de Castro G, Turna H, Cristescu R, Aurora-Garg D, Loboda A, Lunceford J, Kobie J, Ayers M, Pietanza M, Piperdi B, Herbst R. Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC ☆. Annals Of Oncology 2023, 34: 377-388. PMID: 36709038, DOI: 10.1016/j.annonc.2023.01.011.Peer-Reviewed Original ResearchConceptsTissue tumor mutational burdenImproved overall survivalProgression-free survivalTumor mutational burdenOverall survivalKEYNOTE-042Pembrolizumab monotherapyKRAS mutationsClinical utilityMutational burdenMutation statusPD-L1 tumor proportion scoreStandard first-line treatmentEGFR/ALK alterationsAdvanced PD-L1First-line treatmentPD-L1 expressionTumor proportion scorePlatinum-based chemotherapyDeath ligand 1Cell lung cancerPotential predictive biomarkersCut pointsKRAS mutation statusRetrospective exploratory analysis
2022
BFAST but be smart: bTMB remains an exploratory biomarker in NSCLC
Kim SY, Herbst RS. BFAST but be smart: bTMB remains an exploratory biomarker in NSCLC. Nature Reviews Clinical Oncology 2022, 20: 3-4. PMID: 36271141, DOI: 10.1038/s41571-022-00698-y.Peer-Reviewed Original ResearchConceptsCell lung cancerTumor mutational burdenLung cancerMutational burdenBlood-based tumor mutational burdenAdvanced-stage solid tumorsFirst phase III trialHigh tumor mutational burdenImmune checkpoint inhibitorsPhase III trialsIII trialsPredictive biomarkersExploratory biomarkersCompanion biomarkersSolid tumorsBiomarkersCancerBurdenPembrolizumabNSCLCPatientsTumorsTrialsOverall survival from a phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non–small cell lung cancer previously treated with immunotherapy: Lung-MAP nonmatched substudy S1800A.
Reckamp K, Redman M, Dragnev K, Villaruz L, Faller B, Al Baghdadi T, Hines S, Qian L, Minichiello K, Gandara D, Kelly K, Herbst R. Overall survival from a phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non–small cell lung cancer previously treated with immunotherapy: Lung-MAP nonmatched substudy S1800A. Journal Of Clinical Oncology 2022, 40: 9004-9004. DOI: 10.1200/jco.2022.40.16_suppl.9004.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerProgression-free survivalOverall survivalCell lung cancerProgressive diseaseLung cancerLung-MAPImmune checkpoint inhibitor therapyPlatinum-based doublet therapyRandomized phase II trialVEGF receptor inhibitionCheckpoint inhibitor therapyImproved overall survivalPD-L1 expressionPhase II trialPotential survival benefitDuration of responseLog-rank testStandard of careTumor mutational burdenMajor unmet needAnalysis of survivalMultiple tumor typesCare arm
2021
Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1–Positive Advanced NSCLC
Herbst RS, Garon EB, Kim DW, Cho BC, Gervais R, Perez-Gracia JL, Han JY, Majem M, Forster MD, Monnet I, Novello S, Gubens MA, Boyer M, Su WC, Samkari A, Jensen EH, Kobie J, Piperdi B, Baas P. Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1–Positive Advanced NSCLC. Journal Of Thoracic Oncology 2021, 16: 1718-1732. PMID: 34048946, DOI: 10.1016/j.jtho.2021.05.001.Peer-Reviewed Original ResearchConceptsPD-L1 tumor proportion scoreTumor proportion scoreAdvanced NSCLCOverall survivalPembrolizumab improved overall survivalTissue tumor mutational burdenExploratory biomarker analysisImproved overall survivalProgrammed Death LigandTumor mutational burdenDocetaxel 75KEYNOTE-010Pembrolizumab dosesPembrolizumab treatmentSurvival updateData cutoffObjective responseHazard ratioOS ratesCare treatmentLong-term benefitsMedian studyImproved outcomesPembrolizumabProportion score
2020
Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC
Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, Özgüroğlu M, Zou W, Sandler A, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, McCleland M, Mocci S, Jassem J, Spigel DR. Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC. New England Journal Of Medicine 2020, 383: 1328-1339. PMID: 32997907, DOI: 10.1056/nejmoa1917346.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenCarboplatinCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCisplatinDeoxycytidineFemaleGemcitabineHumansLung NeoplasmsMaleMiddle AgedMutationSurvival AnalysisConceptsPD-L1 expressionBlood-based tumor mutational burdenProgression-free survivalPlatinum-based chemotherapyTumor mutational burdenOverall survivalWild-type tumorsAtezolizumab groupChemotherapy groupAdverse eventsPD-L1Mutational burdenHigh PD-L1 expressionPD-L1 expression statusTumor-infiltrating immune cellsMedian overall survivalFirst-line treatmentPD-L1 assaysPhase 3 trialLonger overall survivalSubgroup of patientsCell lung cancerAtezolizumab treatmentSquamous NSCLCTreat populationFrontline immunotherapy for NSCLC — the tale of the tail
Chiang AC, Herbst RS. Frontline immunotherapy for NSCLC — the tale of the tail. Nature Reviews Clinical Oncology 2020, 17: 73-74. PMID: 31907372, DOI: 10.1038/s41571-019-0317-y.Peer-Reviewed Original Research
2019
LBA1 Clinical efficacy of atezolizumab (atezo) in biomarker subgroups by SP142, SP263 and 22C3 PD-L1 immunohistochemistry (IHC) assays and by blood tumour mutational burden (bTMB): Results from the IMpower110 study
Herbst R, de Marinis F, Giaccone G, Reinmuth N, Vergnenegre A, Barrios C, Morise M, Felip E, Andric Z, Geater S, Ozguroglu M, Mocci S, McCleland M, Zou W, Enquist I, Komatsubara K, Deng Y, Kuriki H, Spigel D, Jassem J. LBA1 Clinical efficacy of atezolizumab (atezo) in biomarker subgroups by SP142, SP263 and 22C3 PD-L1 immunohistochemistry (IHC) assays and by blood tumour mutational burden (bTMB): Results from the IMpower110 study. Annals Of Oncology 2019, 30: xi62-xi63. DOI: 10.1093/annonc/mdz453.Peer-Reviewed Original ResearchBlood tumor mutational burdenBiomarker-evaluable populationTumor proportion scorePD-L1Bristol-Myers SquibbClinical trialsF. Hoffmann-La RocheLecture feesAstra ZenecaBoehringer IngelheimHoffmann-La RocheOS HRBiomarker subgroupsPD-L1 IHC assaysPD-L1 immunohistochemistry assaysIHC assaysEli LillyPrincipal investigatorECOG PS 0Genentech/RochePD-L1 cutoffsSignificant OS improvementStage IV NSCLCAstellas PharmaTumor mutational burdenLBA4 Association of KRAS mutational status with response to pembrolizumab monotherapy given as first-line therapy for PD-L1-positive advanced non-squamous NSCLC in Keynote-042
Herbst R, Lopes G, Kowalski D, Kasahara K, Wu Y, De Castro G, Cho B, Turna H, Cristescu R, Aurora-Garg D, Lunceford J, Kobie J, Ayers M, Pietanza M, Piperdi B, Mok T. LBA4 Association of KRAS mutational status with response to pembrolizumab monotherapy given as first-line therapy for PD-L1-positive advanced non-squamous NSCLC in Keynote-042. Annals Of Oncology 2019, 30: xi63-xi64. DOI: 10.1093/annonc/mdz453.001.Peer-Reviewed Original ResearchTumor mutational burdenNon-squamous NSCLCKRAS mutational statusAdvanced non-squamous NSCLCFirst-line therapyWhole-exome sequencingKRAS mutationsPembrolizumab monotherapyPD-L1Mutational statusSubsidiary of MerckBoehringer IngelheimMerck SharpBristol-Myers SquibbDohme Corp.Merck SeronoStandard first-line treatment optionFirst-line treatment optionEli LillyAdvanced PD-L1Genentech/RocheNon-squamous histologyPD-L1 TPSPD-L1 expressionFirst-line treatmentSY6-1 Cancer immunotherapy; A paradigm shift in the first-line treatment of lung cancer
Herbst R. SY6-1 Cancer immunotherapy; A paradigm shift in the first-line treatment of lung cancer. Annals Of Oncology 2019, 30: vi32. DOI: 10.1093/annonc/mdz325.Peer-Reviewed Original ResearchLung cancerImmune checkpoint inhibitorsFirst-line treatmentMinority of patientsTumor mutational burdenPresence of tumorEfficient trial designMarker of resistanceCheckpoint inhibitorsTreatment of cancerCancer deathCancer immunotherapyPredictive markerSmoking ratesMutational burdenNew therapiesTrial designImmune systemCancerTherapyImmunotherapyChemotherapyPatientsTreatmentMarkersImmunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes
Doroshow DB, Sanmamed MF, Hastings K, Politi K, Rimm DL, Chen L, Melero I, Schalper KA, Herbst RS. Immunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes. Clinical Cancer Research 2019, 25: 4592-4602. PMID: 30824587, PMCID: PMC6679805, DOI: 10.1158/1078-0432.ccr-18-1538.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNon-small cell lung cancerImmune checkpoint inhibitorsCell lung cancerPD-L1Lung cancerNonsquamous non-small cell lung cancerOngoing translational workPD-1 axisFirst-line therapyPD-L1 expressionProportion of patientsTumor mutational burdenAdvanced diseaseOverall survivalTumor inflammationMutational burdenPatientsNovel markerChemotherapyTherapyIndicative biomarkersCancerTranslational workBiomarkersSurvivalExpression Analysis and Significance of PD-1, LAG-3, and TIM-3 in Human Non–Small Cell Lung Cancer Using Spatially Resolved and Multiparametric Single-Cell Analysis
Datar I, Sanmamed MF, Wang J, Henick BS, Choi J, Badri T, Dong W, Mani N, Toki M, Mejías L, Lozano MD, Perez-Gracia JL, Velcheti V, Hellmann MD, Gainor JF, McEachern K, Jenkins D, Syrigos K, Politi K, Gettinger S, Rimm DL, Herbst RS, Melero I, Chen L, Schalper KA. Expression Analysis and Significance of PD-1, LAG-3, and TIM-3 in Human Non–Small Cell Lung Cancer Using Spatially Resolved and Multiparametric Single-Cell Analysis. Clinical Cancer Research 2019, 25: 4663-4673. PMID: 31053602, PMCID: PMC7444693, DOI: 10.1158/1078-0432.ccr-18-4142.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDBiomarkers, TumorCarcinoma, Non-Small-Cell LungGene Expression Regulation, NeoplasticHepatitis A Virus Cellular Receptor 2HumansLung NeoplasmsLymphocyte ActivationLymphocyte Activation Gene 3 ProteinLymphocytes, Tumor-InfiltratingPrognosisProgrammed Cell Death 1 ReceptorRetrospective StudiesSingle-Cell AnalysisSurvival RateConceptsNon-small cell lung cancerHuman non-small cell lung cancerTumor-infiltrating lymphocytesAdvanced non-small cell lung cancerTim-3PD-1Cell lung cancerLAG-3Lung cancerPD-1 axis blockadeShorter progression-free survivalBaseline samplesTim-3 protein expressionMajor clinicopathologic variablesMultiplexed quantitative immunofluorescencePD-1 expressionProgression-free survivalTim-3 expressionLAG-3 expressionT-cell phenotypeTumor mutational burdenImmune inhibitory receptorsImmune evasion pathwaysTIM-3 proteinMass cytometry analysis