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
ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA
Remon J, Lacas B, Herbst R, Reck M, Garon EB, Scagliotti GV, Ramlau R, Hanna N, Vansteenkiste J, Yoh K, Groen HJM, Heymach JV, Mandrekar SJ, Okamoto I, Neal JW, Heist RS, Planchard D, Pignon JP, Besse B, group A, Besse B, Lacas B, Pignon J, Remon J, Berghmans T, Dahlberg S, Felip E, Berghmans T, Besse B, Dahlberg S, Felip E, Garon E, Groen H, Hanna N, Heist R, Herbst R, Heymach J, Lacas B, Adjei A, Heist R, Mandrekar S, Neal J, Okamoto I, Pignon J, Ramlau R, Remon J, Reck M, Scagliotti G, Vansteenkiste J, Yoh K. ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA. European Journal Of Cancer 2022, 166: 112-125. PMID: 35286903, DOI: 10.1016/j.ejca.2022.02.002.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerProgression-free survivalAdvanced non-small cell lung cancerFirst-line therapyCell lung cancerIndividual patient dataHazard ratioYounger patientsLung cancerPulmonary thromboembolic eventsPatient dataSecond-line treatmentFirst-line treatmentRisk of hypertensionFixed-effects modelOS benefitPFS benefitThromboembolic eventsOverall survivalSubgroup analysisAntiangiogenicsMeta-AnalysisPatientsMedical needChemotherapy
2021
A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression
Herbst R, Jassem J, Abogunrin S, James D, McCool R, Belleli R, Giaccone G, De Marinis F. A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression. Frontiers In Oncology 2021, 11: 676732. PMID: 34307144, PMCID: PMC8300186, DOI: 10.3389/fonc.2021.676732.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalObjective response rateStage IV non-small cell lung cancerFirst-line treatmentOverall survivalCell lung cancerLung cancerHigh Programmed-Death Ligand 1 (PD-L1) expressionMetastatic non-small cell lung cancerStage non-small cell lung cancerProgrammed Death Ligand 1 ExpressionTreatment-related adverse eventsDeath ligand 1 (PD-L1) expressionPD-L1 expressionPD-L1 statusAbsence of headNetwork Meta-AnalysisRisk of biasRandom-effects modelVersus ChemotherapyImmunotherapy regimenAdverse eventsHead trialsCombination regimens
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 populationO81 IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (ATEZO) monotherapy vs platinum-based chemotherapy (CHEMO) as first-line (1L) treatment in PD-L1–selected NSCLC
Herbst R, De Marinis F, Giaccone G, Reinmuth N, Vergnenegre A, Barrios C, Morise M, Font E, Andric Z, Geater S, Ozguroglu M, Mocci S, McCleland M, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, Jassem J, Spigel D. O81 IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (ATEZO) monotherapy vs platinum-based chemotherapy (CHEMO) as first-line (1L) treatment in PD-L1–selected NSCLC. Journal For ImmunoTherapy Of Cancer 2020, 8: a1. DOI: 10.1136/lba2019.1.Peer-Reviewed Original ResearchTreatment-related AEsPD-L1 expressionPrimary endpointArm APD-L1Interim overall survival analysisTumor PD-L1 statusPD-L1/PDCarboplatin AUC 6ECOG PS 0Primary efficacy populationUnexpected safety signalsFirst-line treatmentPD-L1 statusPhase III studyPlatinum-based chemotherapyWT populationOverall survival analysisDeclaration of HelsinkiAttractive treatment choiceAtezolizumab monotherapyAUC 5AUC 6CPI monotherapyECOG PS
2019
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
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 systemCancerTherapyImmunotherapyChemotherapyPatientsTreatmentMarkersLBA78 IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC
Spigel D, de Marinis F, Giaccone G, Reinmuth N, Vergnenegre A, Barrios C, Morise M, Felip E, Andric Z, Geater S, Özgüroğlu M, Mocci S, McCleland M, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, Jassem J, Herbst R. LBA78 IMpower110: Interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC. Annals Of Oncology 2019, 30: v915. DOI: 10.1093/annonc/mdz293.Peer-Reviewed Original ResearchTreatment-related AEsPD-L1 expressionPD-L1F. Hoffmann-La RocheBristol-Myers SquibbHoffmann-La RocheBoehringer IngelheimArm ACisplatin 75mg/m2Interim overall survival analysisTumor PD-L1 statusTumor-infiltrating immune cellsPD-L1/PDEli LillyCarboplatin AUC 6ECOG PS 0Primary efficacy populationUnexpected safety signalsPD-L1 statusFirst-line treatmentPhase III studyPlatinum-based chemotherapyOverall survival analysisRoche/GenentechBristol-Meyers Squibb
2018
Association of Broad-Based Genomic Sequencing With Survival Among Patients With Advanced Non–Small Cell Lung Cancer in the Community Oncology Setting
Presley CJ, Tang D, Soulos PR, Chiang AC, Longtine JA, Adelson KB, Herbst RS, Zhu W, Nussbaum NC, Sorg RA, Agarwala V, Abernethy AP, Gross CP. Association of Broad-Based Genomic Sequencing With Survival Among Patients With Advanced Non–Small Cell Lung Cancer in the Community Oncology Setting. JAMA 2018, 320: 469-477. PMID: 30088010, PMCID: PMC6142984, DOI: 10.1001/jama.2018.9824.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnaplastic Lymphoma KinaseAntineoplastic AgentsCarcinoma, Non-Small-Cell LungDNA, NeoplasmFemaleGenes, erbB-1GenomicsGenotypeHumansImmunotherapyLung NeoplasmsMaleMiddle AgedMutationNeoplasm StagingReceptor Protein-Tyrosine KinasesRetrospective StudiesSequence Analysis, DNASurvival AnalysisConceptsAdvanced non-small cell lung cancerNon-small cell lung cancerCommunity oncology settingCell lung cancerLung cancerOncology settingRoutine testingNonsquamous non-small cell lung cancerTargeted treatmentPropensity score-matched survival analysisStage IIIB/IVFlatiron Health databaseIIIB/IVRetrospective cohort studyThird-line treatmentFirst-line treatmentMinority of patientsUnadjusted mortality ratesEGFR/ALKCohort studyOverall survivalSecondary outcomesUnmatched cohortPrimary outcomeAntineoplastic treatment
2017
Disparities in next generation sequencing in a population-based community cohort of patients with advanced non-small cell lung cancer.
Presley C, Soulos P, Chiang A, Longtine J, Adelson K, Herbst R, Nussbaum N, Sorg R, Abernethy A, Agarwala V, Gross C. Disparities in next generation sequencing in a population-based community cohort of patients with advanced non-small cell lung cancer. Journal Of Clinical Oncology 2017, 35: 6563-6563. DOI: 10.1200/jco.2017.35.15_suppl.6563.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerNGS testingLung cancerBiomarker testingOncology practiceNext-generation sequencingNon-squamous non-small cell lung cancerPopulation-based community cohortReal-world clinical practiceMulti-gene panel testingInsurance-related disparitiesAdvanced lung cancerFirst-line treatmentHistory of smokingRetrospective observational studyElectronic health record dataWorld clinical practiceClustering of patientsHealth record dataYounger patientsMedian agePatient characteristicsWhite patients
2011
Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial
Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, Vlahovic G, Soh CH, O'Connor P, Hainsworth J. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. The Lancet 2011, 377: 1846-1854. PMID: 21621716, PMCID: PMC4134127, DOI: 10.1016/s0140-6736(11)60545-x.Peer-Reviewed Original ResearchMeSH KeywordsAgedAngiogenesis InhibitorsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Non-Small-Cell LungDisease-Free SurvivalDouble-Blind MethodErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMiddle AgedProportional Hazards ModelsProtein Kinase InhibitorsQuinazolinesSurvival RateVascular Endothelial Growth Factor AConceptsPhase 3 trialBevacizumab groupCell lung cancerAdverse eventsOverall survivalRefractory NSCLCPrimary endpointLung cancerControl groupComputer-generated randomisation sequenceGrade 5 adverse eventsStandard first-line chemotherapyCalculation of incidenceEfficacy of bevacizumabArterial thromboembolic eventsFirst-line chemotherapyMedian overall survivalObjective response rateSerious adverse eventsAddition of bevacizumabFirst-line treatmentPhase 1/2 trialProgression-free survivalToxic effect profilesActivity of erlotinib
2009
Safety of bevacizumab (B) and erlotinib (E) therapy in patients (pts) with treated brain metastases (mets) in the phase III, placebo (P)-controlled, randomized BeTa trial for pts with advanced non-small cell lung cancer (NSCLC) after failure of standard first-line chemotherapy
Otterson G, O’Connor P, Lin M, Herbst R. Safety of bevacizumab (B) and erlotinib (E) therapy in patients (pts) with treated brain metastases (mets) in the phase III, placebo (P)-controlled, randomized BeTa trial for pts with advanced non-small cell lung cancer (NSCLC) after failure of standard first-line chemotherapy. Journal Of Clinical Oncology 2009, 27: e19025-e19025. DOI: 10.1200/jco.2009.27.15_suppl.e19025.Peer-Reviewed Original ResearchNon-small cell lung cancerBrain metsBrain metastasesAdverse eventsTreatment durationAdvanced non-small cell lung cancerAdvanced stage non-small cell lung cancerStage non-small cell lung cancerEpidermal growth factor receptor-targeted therapyLung StudyNervous system adverse eventsStandard first-line chemotherapyWhole-brain radiation therapySafety of bevacizumabSubset of ptsCarboplatin/paclitaxelFirst-line chemotherapyMedian treatment durationAcceptable safety profileAdvanced NSCLC patientsBrain radiation therapyFirst-line treatmentNew safety signalsSubset of patientsReceptor-targeted therapyBeyond Doublet Chemotherapy for Advanced Non–Small-Cell Lung Cancer: Combination of Targeted Agents with First-Line Chemotherapy
Herbst RS, Lynch TJ, Sandler AB. Beyond Doublet Chemotherapy for Advanced Non–Small-Cell Lung Cancer: Combination of Targeted Agents with First-Line Chemotherapy. Clinical Lung Cancer 2009, 10: 20-27. PMID: 19289368, DOI: 10.3816/clc.2009.n.003.Peer-Reviewed Original ResearchConceptsBest supportive careOverall survivalMetastatic NSCLCLung cancerAdvanced non-small cell lung cancerNon-small cell lung cancerPhase III clinical trialsPlatinum-based doubletsAddition of bevacizumabFirst-line chemotherapyPlatinum-based regimensProgression-free survivalFirst-line treatmentCell lung cancerOverall patient survivalTyrosine kinase inhibitorsInhibition of componentsMatrix metalloproteinase inhibitorsDoublet chemotherapySystemic chemotherapyMedian survivalSupportive careMost patientsTargeted agentsChemotherapeutic regimens
2007
Phase II study of bevacizumab in combination with docetaxel and carboplatin in patients with metastatic non-small cell lung cancer (NSCLC)
William W, Kies M, Fossella F, Gladish G, Heymach J, Glisson B, Tse W, Liu D, Herbst R, Lippman S. Phase II study of bevacizumab in combination with docetaxel and carboplatin in patients with metastatic non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2007, 25: 18098-18098. DOI: 10.1200/jco.2007.25.18_suppl.18098.Peer-Reviewed Original ResearchNon-small cell lung cancerMetastatic non-small cell lung cancerCombination of bevacizumabProgression-free survivalSevere adverse eventsStage IIIBPS 0Incurable non-small cell lung cancerChemotherapy-naïve stage IIIBNon-squamous cell histologyMedian age 66 yearsCarboplatin AUC 6Cycles of therapyDisease control rateEfficacy of bevacizumabFull-dose anticoagulationGrade 3 hypertensionHistory of hemoptysisStable cardiac conditionPhase II studyPhase II trialAge 66 yearsFirst-line treatmentCell lung cancerAUC 6Randomized phase II study of vandetanib (VAN) alone or in combination with carboplatin and paclitaxel (CP) as first-line treatment for advanced non-small cell lung cancer (NSCLC)
Heymach J, Paz-Ares L, De Braud F, Sebastian M, Stewart D, Eberhardt W, Herbst R, Krebs A, Langmuir P, Johnson B. Randomized phase II study of vandetanib (VAN) alone or in combination with carboplatin and paclitaxel (CP) as first-line treatment for advanced non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2007, 25: 7544-7544. DOI: 10.1200/jco.2007.25.18_suppl.7544.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalAdvanced non-small cell lung cancerRandomized phase II trialPhase II trialOverall survivalII trialMedian progression-free survivalRandomized phase II studyCTC grade 2Daily oral agentObjective response ratePlasma angiogenic factorsPhase II studyFirst-line treatmentCell lung cancerExploratory subgroup analysisFemale ptsCNS metastasesEligible patientsMonotherapy armSecondary endpointsSquamous histologyII studyOral agents
2006
Use of Novel Second-Line Targeted Therapies in Non–Small Cell Lung Cancer
Massarelli E, Herbst RS. Use of Novel Second-Line Targeted Therapies in Non–Small Cell Lung Cancer. Seminars In Oncology 2006, 33: 9-16. PMID: 16472704, DOI: 10.1053/j.seminoncol.2005.12.007.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerOverall response rateEpidermal growth factor receptorCell lung cancerLung cancerResponse rateSecond-line therapeutic approachStandard cytotoxic regimensFirst-line treatmentNew treatment optionsLung cancer casesQuality of lifeNew chemotherapeutic agentsCytotoxic regimensGrowth factor receptorRefractory settingMetastatic diseaseRefractory diseaseLocal therapyNSCLC treatmentTreatment optionsCancer deathTargeted therapyTreatment outcomesCancer cases
2005
Phase II study of pemetrexed in combination with carboplatin in the first‐line treatment of advanced nonsmall cell lung cancer
Zinner RG, Fossella FV, Gladish GW, Glisson BS, Blumenschein GR, Papadimitrakopoulou VA, Pisters KM, Kim ES, Oh YW, Peeples BO, Ye Z, Curiel RE, Obasaju CK, Hong WK, Herbst RS. Phase II study of pemetrexed in combination with carboplatin in the first‐line treatment of advanced nonsmall cell lung cancer. Cancer 2005, 104: 2449-2456. PMID: 16258975, DOI: 10.1002/cncr.21480.Peer-Reviewed Original ResearchConceptsAdvanced nonsmall cell lung cancerNonsmall cell lung cancerCell lung cancerPerformance statusLung cancerSerum concentration-time curveGrade 3/4 thrombocytopeniaNonhematologic side effectsZubrod performance statusGrade 3/4 neutropeniaPartial response ratePercent of patientsPhase II studyStage IV diseaseFirst-line therapyFirst-line treatmentConcentration-time curveCarboplatin areaPrior chemotherapyStage IIIBII studyMedian ageMedian timeSensory neuropathyMedian numberP-497 ZD6474 in combination with carboplatin and paclitaxel as first-line treatment in patients with NSCLC: Results of the run-in phase of a two-part randomized Phase II study
Hevmach J, West H, Kerr R, Prager D, Sandler A, Herbst R, Stewart D, Dimery I, Johnson B. P-497 ZD6474 in combination with carboplatin and paclitaxel as first-line treatment in patients with NSCLC: Results of the run-in phase of a two-part randomized Phase II study. Lung Cancer 2005, 49: s247. DOI: 10.1016/s0169-5002(05)80990-0.Peer-Reviewed Original Research
2004
Evaluation of epidermal growth factor receptor (EGFR) as a prognostic factor for survival in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy as first-line treatment
Janas M, Bailey L, Schmidt K, Bindslev N, Wolf M, Fandi A, Askaa J, Herbst R, Giaccone G, Johnson D. Evaluation of epidermal growth factor receptor (EGFR) as a prognostic factor for survival in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy as first-line treatment. Journal Of Clinical Oncology 2004, 22: 7024-7024. DOI: 10.1200/jco.2004.22.14_suppl.7024.Peer-Reviewed Original ResearchEvaluation of epidermal growth factor receptor (EGFR) as a prognostic factor for survival in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy as first-line treatment
Janas M, Bailey L, Schmidt K, Bindslev N, Wolf M, Fandi A, Askaa J, Herbst R, Giaccone G, Johnson D. Evaluation of epidermal growth factor receptor (EGFR) as a prognostic factor for survival in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy as first-line treatment. Journal Of Clinical Oncology 2004, 22: 7024-7024. DOI: 10.1200/jco.2004.22.90140.7024.Peer-Reviewed Original Research