2022
Phase II Randomized Study of Ramucirumab and Pembrolizumab Versus Standard of Care in Advanced Non–Small-Cell Lung Cancer Previously Treated With Immunotherapy—Lung-MAP S1800A
Reckamp KL, Redman MW, Dragnev KH, Minichiello K, Villaruz LC, Faller B, Al Baghdadi T, Hines S, Everhart L, Highleyman L, Papadimitrakopoulou V, Neal J, Waqar SN, Patel JD, Gray JE, Gandara DR, Kelly K, Herbst RS. Phase II Randomized Study of Ramucirumab and Pembrolizumab Versus Standard of Care in Advanced Non–Small-Cell Lung Cancer Previously Treated With Immunotherapy—Lung-MAP S1800A. Journal Of Clinical Oncology 2022, 40: 2295-2306. PMID: 35658002, PMCID: PMC9287284, DOI: 10.1200/jco.22.00912.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionInvestigator-assessed progression-free survivalProgression-free survivalOverall survivalVascular endothelial growth factorLung cancerAdvanced non-small cell lung cancerNon-small cell lung cancerPhase II Randomized StudyTreatment-related adverse eventsRandomized phase II trialSecondary end pointsPhase II trialPlatinum-based chemotherapyCell lung cancerDuration of responseLog-rank testMajor unmet needEndothelial growth factorMultiple tumor typesAdvanced NSCLCEligible patientsOS benefitII trialObjective response
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
2019
Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial
Herbst RS, Baas P, Perez-Gracia JL, Felip E, Kim D, Han J, Molina JR, Kim J, Arvis C, Ahn M, Majem M, Fidler MJ, Surmont V, de Castro G, Garrido M, Shentu Y, Emancipator K, Samkari A, Jensen EH, Lubiniecki GM, Garon EB. Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Annals Of Oncology 2019, 30: 281-289. PMID: 30657853, PMCID: PMC6931268, DOI: 10.1093/annonc/mdy545.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiopsyCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellDocetaxelFemaleFollow-Up StudiesHumansInternational AgenciesLung NeoplasmsMaleMiddle AgedParaffin EmbeddingPrognosisSpecimen HandlingSurvival RateYoung AdultConceptsTumor proportion scoreOS hazard ratioPD-L1 expressionProgression-free survivalPFS hazard ratioHazard ratioOverall survivalTumor samplesPD-L1PD-L1 tumor proportion scorePrespecified exploratory analysisPrimary end pointSubset of patientsCell lung cancerDeath 1 proteinArchival samplesDocetaxel 75KEYNOTE-010Pembrolizumab dosesRECIST v1.1Advanced NSCLCLung cancerProportion scorePatientsPrimary analysisHealth-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced, Programmed Death Ligand 1–Expressing NSCLC
Barlesi F, Garon E, Kim D, Felip E, Han J, Kim J, Ahn M, Fidler M, Gubens M, de Castro G, Surmont V, Li Q, Deitz A, Lubiniecki G, Herbst R. Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced, Programmed Death Ligand 1–Expressing NSCLC. Journal Of Thoracic Oncology 2019, 14: 793-801. PMID: 30711649, DOI: 10.1016/j.jtho.2019.01.016.Peer-Reviewed Original ResearchConceptsGlobal health statusDeath ligand 1Composite endpointPhase II/III studyGHS/QoL scoresLife Questionnaire Core 30Programmed Death Ligand 1Symptom domainsNSCLC patient populationPembrolizumab-treated patientsWeek 12 changesHealth-related qualityLigand 1Quality of lifeGHS/KEYNOTE-010Advanced NSCLCChest painIII studyOverall survivalCancer QualityEuroQol-5D.Life scoresMean baselinePatient population
2017
Immunotherapy in Lung Cancer
Du L, Herbst RS, Morgensztern D. Immunotherapy in Lung Cancer. Hematology/Oncology Clinics Of North America 2017, 31: 131-141. PMID: 27912829, DOI: 10.1016/j.hoc.2016.08.004.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerAdvanced stage non-small cell lung cancerPD-1/PD-L1 axisFirst-line platinum-based doubletStage non-small cell lung cancerApproval of nivolumabPlatinum-based doubletsSecond-line docetaxelGood performance statusImmune checkpoint inhibitorsPD-L1 axisMinority of patientsRandomized clinical trialsTreatment of patientsNew therapeutic approachesClass of drugsCheckpoint inhibitorsOverall survivalPerformance statusClinical trialsProlonged benefitTherapeutic approachesPatients
2015
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial
Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. The Lancet 2015, 387: 1540-1550. PMID: 26712084, DOI: 10.1016/s0140-6736(15)01281-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsB7-H1 AntigenCarcinoma, Non-Small-Cell LungDisease-Free SurvivalDocetaxelDrug Administration ScheduleFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedMolecular Targeted TherapyPatient SelectionTaxoidsTreatment OutcomeConceptsCell lung cancerProgression-free survivalPD-L1 expressionOverall survivalLung cancerPD-L1Tumor cellsMedian progression-free survivalTreatment-related adverse eventsEfficacy of pembrolizumabMedian overall survivalProlongs overall survivalNew treatment optionsAcademic medical centerPrimary endpointAdverse eventsProgressive diseasePatient populationTotal populationTreatment optionsPembrolizumabGrade 3Medical CenterEffective treatmentInteractive voice response system
2014
EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer
Heymach JV, Lockwood SJ, Herbst RS, Johnson BE, Ryan AJ. EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer. Annals Of Oncology 2014, 25: 1941-1948. PMID: 25057173, PMCID: PMC4176452, DOI: 10.1093/annonc/mdu269.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSecond-line treatmentProgression-free survivalAdvanced non-small cell lung cancerRandomized phase III studyPhase III studyCell lung cancerMutation-positive tumorsEGFR mutationsIII studyTumor samplesClinical benefitLung cancerSecond-line non-small cell lung cancerEGFR FISH-positive tumorsEGFR mutation-positive tumorsEpidermal growth factor receptor (EGFR) gene mutationsObjective response rateRelative clinical benefitFirst-line chemotherapyObjective tumor responseProtein expressionOverall study populationGene mutationsPretreatment tumor samples
2012
A step towards treating KRAS-mutant NSCLC
Goldberg SB, Schlessinger J, Boyer JL, Herbst RS. A step towards treating KRAS-mutant NSCLC. The Lancet Oncology 2012, 14: 3-5. PMID: 23200176, DOI: 10.1016/s1470-2045(12)70528-4.Peer-Reviewed Original ResearchPhase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours
Martin LP, Kozloff MF, Herbst RS, Samuel TA, Kim S, Rosbrook B, Tortorici M, Chen Y, Tarazi J, Olszanski AJ, Rado T, Starr A, Cohen RB. Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours. British Journal Of Cancer 2012, 107: 1268-1276. PMID: 22996612, PMCID: PMC3494424, DOI: 10.1038/bjc.2012.407.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsCommon treatment-related adverse eventsSolid tumorsTreatment-related adverse eventsAntitumour activitySelective second-generation inhibitorPhase ICo-administered agentsVascular endothelial growth factor receptorHand-foot syndromeEndothelial growth factor receptorHuman xenograft tumor modelsEfficacy of chemotherapyXenograft tumor modelMultiple tumor typesAxitinib pharmacokineticsCapecitabine pharmacokineticsGrowth factor receptorStable diseaseStarting doseAdverse eventsPartial responseComplete responseTreatment regimenDocetaxel exposure
2010
Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial
Herbst RS, Sun Y, Eberhardt W, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. The Lancet Oncology 2010, 11: 619-626. PMID: 20570559, PMCID: PMC3225192, DOI: 10.1016/s1470-2045(10)70132-7.Peer-Reviewed Original ResearchConceptsProgression-free survivalMedian progression-free survivalVascular endothelial growth factor receptorCell lung cancerEpidermal growth factor receptorVandetanib groupFebrile neutropeniaGrowth factor receptorPlacebo groupAdverse eventsLung cancerCommon serious adverse eventsDefinitive phase 3 trialLonger progression-free survivalComparison of PFSDaily oral inhibitorHigher adverse eventsSecond-line treatmentFirst-line chemotherapyFirst-line therapyPhase 2 studyPhase 3 trialSerious adverse eventsFactor receptorEndothelial growth factor receptorPhase II Study of Vinorelbine and Docetaxel in the Treatment of Advanced Non–Small-Cell Lung Cancer as Frontline and Second-Line Therapy
William WN, Khuri FR, Fossella FV, Glisson BS, Zinner RG, Lee JJ, Herbst RS, Lippman SM, Kim ES. Phase II Study of Vinorelbine and Docetaxel in the Treatment of Advanced Non–Small-Cell Lung Cancer as Frontline and Second-Line Therapy. American Journal Of Clinical Oncology 2010, 33: 148-152. PMID: 19687727, PMCID: PMC5118944, DOI: 10.1097/coc.0b013e318199fb99.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBone NeoplasmsCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellDocetaxelFemaleFollow-Up StudiesHumansLung NeoplasmsMaleMiddle AgedNeoplasm StagingSalvage TherapySurvival RateTaxoidsTreatment OutcomeVinblastineVinorelbineConceptsCell lung cancerLung cancerGrade 3Advanced non-small cell lung cancerNon-small cell lung cancerCommon grade 3Experienced febrile neutropeniaFirst-line settingMedian overall survivalNausea/vomitingSecond-line patientsSecond-line settingSecond-line therapyPhase 2 studyPhase II studySingle-agent chemotherapyUse of docetaxelCombination of docetaxelFrontline treatment optionFilgrastim supportNonplatinum agentsFebrile neutropeniaNonhematologic toxicitySalvage therapyII study
2009
A phase 2 study of cetuximab in combination with docetaxel in chemotherapy‐refractory/resistant patients with advanced nonsmall cell lung cancer
Kim ES, Mauer AM, William WN, Tran HT, Liu D, Lee JJ, Windt P, Hong WK, Vokes EE, Herbst RS. A phase 2 study of cetuximab in combination with docetaxel in chemotherapy‐refractory/resistant patients with advanced nonsmall cell lung cancer. Cancer 2009, 115: 1713-1722. PMID: 19208430, PMCID: PMC5142442, DOI: 10.1002/cncr.24148.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCetuximabDisease ProgressionDocetaxelDrug Administration ScheduleErbB ReceptorsFemaleHumansLung NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalTaxoidsConceptsNonsmall cell lung cancerAdvanced nonsmall cell lung cancerResponse rateOverall survivalResistant patientsLung cancerEpidermal growth factor receptor expressionCommon grade 3Growth factor receptor expressionMedian overall survivalSecond-line settingPhase 2 studyCell lung cancerTarget sample sizeFactor receptor expressionStable diseaseAdverse eventsPartial responseComplete responseDisease recurrenceMedian timeDisease progressionReceptor expressionAllergic reactionsGrade 3
2007
Phase II Study of Efficacy and Safety of Bevacizumab in Combination With Chemotherapy or Erlotinib Compared With Chemotherapy Alone for Treatment of Recurrent or Refractory Non–Small-Cell Lung Cancer
Herbst RS, O'Neill VJ, Fehrenbacher L, Belani CP, Bonomi PD, Hart L, Melnyk O, Ramies D, Lin M, Sandler A. Phase II Study of Efficacy and Safety of Bevacizumab in Combination With Chemotherapy or Erlotinib Compared With Chemotherapy Alone for Treatment of Recurrent or Refractory Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2007, 25: 4743-4750. PMID: 17909199, DOI: 10.1200/jco.2007.12.3026.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma, Bronchiolo-AlveolarAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Large CellCarcinoma, Non-Small-Cell LungDisease-Free SurvivalDocetaxelErlotinib HydrochlorideFemaleGlutamatesGuanineHumansLung NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPemetrexedQuinazolinesSurvival RateTaxoidsTreatment OutcomeConceptsProgression-free survivalAdverse eventsLung cancerHumanized anti-vascular endothelial growth factor monoclonal antibodyRefractory non-small cell lung cancerAnti-vascular endothelial growth factor monoclonal antibodyEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsNon-small cell lung cancerSingle-arm phase IRandomized phase II trialOne-year survival rateReceptor tyrosine kinase inhibitorsFatal pulmonary hemorrhagePlatinum-based regimenSafety of bevacizumabStudies of bevacizumabUnexpected safety signalsPhase II studySecond-line settingPhase II trialTreatment of recurrentCell lung cancerFactor monoclonal antibodyFavorable safety profileRandomized, Placebo-Controlled Phase II Study of Vandetanib Plus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer
Heymach JV, Johnson BE, Prager D, Csada E, Roubec J, Pešek M, Špásová I, Belani CP, Bodrogi I, Gadgeel S, Kennedy SJ, Hou J, Herbst RS. Randomized, Placebo-Controlled Phase II Study of Vandetanib Plus Docetaxel in Previously Treated Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2007, 25: 4270-4277. PMID: 17878479, DOI: 10.1200/jco.2006.10.5122.Peer-Reviewed Original ResearchConceptsProgression-free survivalRandomized phaseOverall survivalLung cancerFirst-line platinum-based chemotherapyNon-small cell lung cancerMedian progression-free survivalActivity of vandetanibCommon adverse eventsDaily oral inhibitorObjective response rateOpen-label runPhase II studyGrowth factor receptor 2Platinum-based chemotherapyCell lung cancerOne-sided significance levelEndothelial growth factor receptor 2Second-line NSCLCVascular endothelial growth factor receptor 2Factor receptor 2Asymptomatic prolongationEligible patientsMetastatic NSCLCII study
2005
Therapeutic Strategies for Combined-Modality Therapy of Locally Advanced-Stage Non–Small-Cell Lung Cancer: Rationale for Consolidation Docetaxel Therapy
Gandara DR, Vallières E, Gaspar LE, Kelly K, Albain KS, Herbst RS, Lara PN, Mack P, Gumerlock PH, Crowley JJ. Therapeutic Strategies for Combined-Modality Therapy of Locally Advanced-Stage Non–Small-Cell Lung Cancer: Rationale for Consolidation Docetaxel Therapy. Clinical Lung Cancer 2005, 7: s93-s97. PMID: 16384543, DOI: 10.3816/clc.2005.s.017.Peer-Reviewed Original ResearchConceptsCell lung cancerRadiation therapyDocetaxel therapyLung cancerChemotherapy/radiation therapyGood performance statusCombined modality therapyThoracic radiation therapyRecent clinical trialsStandard of careCombination of chemotherapyPerformance statusDose scheduleTreatment paradigmClinical trialsTherapeutic strategiesTherapyCancerChemotherapyPatientsTrialsCare
2004
EGFR inhibition in NSCLC: the emerging role of cetuximab.
Herbst RS. EGFR inhibition in NSCLC: the emerging role of cetuximab. Journal Of The National Comprehensive Cancer Network 2004, 2 Suppl 2: s41-51. PMID: 19780245.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerEpidermal growth factor receptor inhibitorsGrowth factor receptor inhibitorsCell lung cancerTyrosine kinase inhibitorsLung cancerReceptor inhibitorsKinase inhibitorsAdvanced non-small cell lung cancerMonoclonal antibodiesEpidermal growth factor receptor expressionChemotherapy-related toxicityGrowth factor receptor expressionGrowth factor receptor inhibitionRole of cetuximabPhase II trialInterstitial lung diseaseEpidermal growth factor receptor inhibitionOverall response rateFactor receptor expressionModerate rashII trialUntreated patientsHypersensitivity reactionsLung disease
2003
Mode of action of docetaxel – a basis for combination with novel anticancer agents
Herbst RS, Khuri FR. Mode of action of docetaxel – a basis for combination with novel anticancer agents. Cancer Treatment Reviews 2003, 29: 407-415. PMID: 12972359, DOI: 10.1016/s0305-7372(03)00097-5.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsApoptosisDocetaxelDrug Resistance, NeoplasmDrug SynergismErbB ReceptorsFemaleFollow-Up StudiesHumansMaleNeoplasmsNeovascularization, PathologicPaclitaxelPharmacogeneticsSurvival AnalysisTaxoidsTreatment OutcomeConceptsPatient populationOptimal treatment strategySpecific patient populationsCertain chemotherapeutic drugsAnticancer agentsOptimal therapySpecific therapyTreatment strategiesNovel agentsClinical investigationNew anticancer agentsNovel anticancer agentsCancer growthDifferent tumorsStimulation pathwayChemotherapeutic drugsInhibitor of mitosisAntitumor activityTumorigenic mechanismsMode of actionAgent combinationsDocetaxelTherapyAgentsDifferent aberrationsInduction docetaxel and carboplatin followed by weekly docetaxel and carboplatin with concurrent radiotherapy, then surgery in stage III non-small cell lung cancer: a Phase I study.
Wirth LJ, Lucca J, Ostler P, Fidias P, Lynch C, Jänne PA, Herbst RS, Johnson BE, Sugarbaker DJ, Mathisen DJ, Lukanich JM, Choi NC, Berman SM, Skarin AT. Induction docetaxel and carboplatin followed by weekly docetaxel and carboplatin with concurrent radiotherapy, then surgery in stage III non-small cell lung cancer: a Phase I study. Clinical Cancer Research 2003, 9: 1698-704. PMID: 12738723.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerStage III non-small cell lung cancerCT/RTMaximum-tolerated doseCell lung cancerConcurrent radiotherapyLung cancerDose levelsConcurrent weekly carboplatinGrade 3 toxicityPathologic complete responsePhase II studyInduction docetaxelTrimodality treatmentWeekly carboplatinWeekly docetaxelII studyOverall survivalStage IIIAComplete responseSurgical patientsSubsequent radiotherapyNew regimenInduction CTGrade 3A retrospective analysis of the outcome of patients who have received two prior chemotherapy regimens including platinum and docetaxel for recurrent non-small-cell lung cancer
Massarelli E, Andre F, Liu DD, Lee JJ, Wolf M, Fandi A, Ochs J, Le Chevalier T, Fossella F, Herbst RS. A retrospective analysis of the outcome of patients who have received two prior chemotherapy regimens including platinum and docetaxel for recurrent non-small-cell lung cancer. Lung Cancer 2003, 39: 55-61. PMID: 12499095, DOI: 10.1016/s0169-5002(02)00308-2.Peer-Reviewed Original ResearchConceptsMedian overall survival timePrior chemotherapy regimensSecond-line treatmentCell lung cancerOverall survival timeChemotherapy regimensLung cancerChemotherapy agentsRetrospective analysisSurvival timeDisease control rateFourth-line chemotherapyFourth-line treatmentOverall performance statusSecond-line therapyStage III diseaseStage IV diseaseOutcomes of patientsDays of chemotherapyFirst-line treatmentLine of treatmentEuropean cancer centersNovel therapy approachesRecurrent NSCLCAdvanced NSCLC