2014
“Companion Diagnostics”: Has Their Time Come and Gone?
Hirsch FR, Bunn PA, Herbst RS. “Companion Diagnostics”: Has Their Time Come and Gone? Clinical Cancer Research 2014, 20: 4422-4424. PMID: 25059519, PMCID: PMC4155019, DOI: 10.1158/1078-0432.ccr-14-0932.Peer-Reviewed Original Research
2013
Phase I–IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours
Soria JC, Baselga J, Hanna N, Laurie SA, Bahleda R, Felip E, Calvo E, Armand JP, Shepherd FA, Harbison CT, Berman D, Park JS, Zhang S, Vakkalagadda B, Kurland JF, Pathak AK, Herbst RS. Phase I–IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours. European Journal Of Cancer 2013, 49: 1815-1824. PMID: 23490650, DOI: 10.1016/j.ejca.2013.02.012.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedArea Under CurveCarcinoma, Non-Small-Cell LungDiarrheaDose-Response Relationship, DrugDrug Resistance, NeoplasmErbB ReceptorsErlotinib HydrochlorideExanthemaFemaleHumansLung NeoplasmsMaleMetabolic Clearance RateMiddle AgedNeoplasm MetastasisNeoplasmsPiperidinesProtein Kinase InhibitorsPyrrolesQuinazolinesReceptor, ErbB-2Treatment OutcomeTriazinesVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-3ConceptsIIa studyBMS-690514Growth factor receptorPhase IAdverse eventsEGFR mutationsHER-2Phase IIaFrequent treatment-related adverse eventsSolid tumorsTreatment-related adverse eventsOral tyrosine kinase inhibitorDisease controlVascular endothelial growth factor receptorManageable safety profileObjective response rateAdvanced solid tumorsFactor receptorMetastatic solid tumorsEndothelial growth factor receptorCell lung cancerTyrosine kinase inhibitorsInhibition of VEGFREpidermal growth factor receptorWild-type EGFR
2012
Clinical Outcomes and Biomarker Profiles of Elderly Pretreated NSCLC Patients from the BATTLE Trial
Tsao AS, Liu S, Lee JJ, Alden C, Blumenschein G, Herbst R, Davis SE, Kim E, Lippman S, Stewart D, Tang XM, Wistuba I, Hong WK. Clinical Outcomes and Biomarker Profiles of Elderly Pretreated NSCLC Patients from the BATTLE Trial. Journal Of Thoracic Oncology 2012, 7: 1645-1652. PMID: 23059780, PMCID: PMC5161038, DOI: 10.1097/jto.0b013e31826910ff.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBexaroteneBiomarkers, TumorCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellDrug Resistance, NeoplasmErlotinib HydrochlorideFemaleFollow-Up StudiesHumansLung NeoplasmsMaleMiddle AgedNeoplasm StagingNiacinamidePhenylurea CompoundsPiperidinesPrognosisQuinazolinesRetrospective StudiesSalvage TherapySorafenibSurvival RateTetrahydronaphthalenesConceptsProgression-free survivalDisease control rateNSCLC patientsOverall survivalElderly menGrade 3Older womenOlder menBetter median progression-free survivalHigher disease control rateLung Cancer Elimination (BATTLE) trialMedian progression-free survivalAge groupsBetter progression-free survivalCell lung cancer patientsBiomarker-Integrated ApproachesBiopsy-related pneumothoraxElderly NSCLC patientsMore grade 3Treatment-related deathsTumor tissue biomarkersRetrospective subgroup analysisSubset of patientsHigher overall survivalLung cancer 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
2010
Phase II Selection Design Trial of Concurrent Chemotherapy and Cetuximab Versus Chemotherapy Followed by Cetuximab in Advanced-Stage Non–Small-Cell Lung Cancer: Southwest Oncology Group Study S0342
Herbst RS, Kelly K, Chansky K, Mack PC, Franklin WA, Hirsch FR, Atkins JN, Dakhil SR, Albain KS, Kim ES, Redman M, Crowley JJ, Gandara DR. Phase II Selection Design Trial of Concurrent Chemotherapy and Cetuximab Versus Chemotherapy Followed by Cetuximab in Advanced-Stage Non–Small-Cell Lung Cancer: Southwest Oncology Group Study S0342. Journal Of Clinical Oncology 2010, 28: 4747-4754. PMID: 20921467, PMCID: PMC3020704, DOI: 10.1200/jco.2009.27.9356.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinCarcinoma, Non-Small-Cell LungCetuximabDisease-Free SurvivalDrug Administration ScheduleErbB ReceptorsErlotinib HydrochlorideFemaleHumansKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedMutationNeoplasm StagingPaclitaxelPatient SelectionProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsResearch DesignSouthwestern United StatesTreatment OutcomeConceptsCell lung cancerConcurrent chemotherapyLung cancerEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsProgression-free survival timeRandomized phase II trialReceptor tyrosine kinase inhibitorsMedian overall survivalPaclitaxel/carboplatinTreatment-naive patientsGrade 3 rashPhase II trialAdvanced-stage NSCLCPhase III evaluationTyrosine kinase inhibitorsEnhanced antitumor activityConcurrent regimenMaintenance cetuximabMedian followVersus ChemotherapyChemotherapy regimenII trialSequential therapyConcurrent therapyA Multicenter, Phase 2 Study of Vascular Endothelial Growth Factor Trap (Aflibercept) in Platinum- and Erlotinib-Resistant Adenocarcinoma of the Lung
Leighl NB, Raez LE, Besse B, Rosen PJ, Barlesi F, Massarelli E, Gabrail N, Hart LL, Albain KS, Berkowitz L, Melnyk O, Shepherd FA, Sternas L, Ackerman J, Shun Z, Miller VA, Herbst RS. A Multicenter, Phase 2 Study of Vascular Endothelial Growth Factor Trap (Aflibercept) in Platinum- and Erlotinib-Resistant Adenocarcinoma of the Lung. Journal Of Thoracic Oncology 2010, 5: 1054-1059. PMID: 20593550, DOI: 10.1097/jto.0b013e3181e2f7fb.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMiddle AgedOrganoplatinum CompoundsQuinazolinesReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsSalvage TherapySurvival RateTreatment OutcomeConceptsProgression-free survivalLung adenocarcinomaLung cancerResponse rateCommon grade 3/4 toxicitiesMedian progression-free survivalVascular endothelial growth factor trapGrade 5 hemoptysisReversible posterior leukoencephalopathyGrade 3/4 toxicitiesPrimary end pointPhase 2 studyPhase I trialSingle-agent activityDuration of responseOverall response ratePlacental growth factorCardiac ejection fractionProgression of diseaseActivity of VEGFIntravenous afliberceptPosterior leukoencephalopathyIntolerable toxicityOverall survivalCerebral ischemiaPharmacokinetic study of the phase III, randomized, double-blind, multicenter trial (TRIBUTE) of paclitaxel and carboplatin combined with erlotinib or placebo in patients with advanced Non-small Cell Lung Cancer (NSCLC)
Tran HT, Zinner RG, Blumenschein GR, Oh YW, Papadimitrakopoulou VA, Kim ES, Lu C, Malik M, Lum BL, Herbst RS. Pharmacokinetic study of the phase III, randomized, double-blind, multicenter trial (TRIBUTE) of paclitaxel and carboplatin combined with erlotinib or placebo in patients with advanced Non-small Cell Lung Cancer (NSCLC). Investigational New Drugs 2010, 29: 499-505. PMID: 20094773, DOI: 10.1007/s10637-009-9380-z.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerDrug-drug interactionsErlotinib groupPlacebo groupPotential drug-drug interactionsErlotinib treatment groupPlacebo-treated patientsPossible drug-drug interactionsStandard chemotherapy regimenPhase III trialsCell lung cancerAddition of erlotinibPharmacokinetics of erlotinibMetabolite OSI-420Non-compartmental modelingAUC 6Erlotinib 150Paclitaxel 200Resultant paclitaxelChemotherapy regimenIII trialsUntreated patientsConcomitant administrationMulticenter trial
2009
VeriStrat® classifier for survival and time to progression in non-small cell lung cancer (NSCLC) patients treated with erlotinib and bevacizumab
Carbone DP, Salmon JS, Billheimer D, Chen H, Sandler A, Roder H, Roder J, Tsypin M, Herbst RS, Tsao AS, Tran HT, Dang TP. VeriStrat® classifier for survival and time to progression in non-small cell lung cancer (NSCLC) patients treated with erlotinib and bevacizumab. Lung Cancer 2009, 69: 337-340. PMID: 20036440, PMCID: PMC2891357, DOI: 10.1016/j.lungcan.2009.11.019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Non-Small-Cell LungDisease ProgressionDisease-Free SurvivalErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMass SpectrometryMiddle AgedNeoplasm Recurrence, LocalPrecision MedicinePredictive Value of TestsProteomeQuinazolinesConceptsNon-small cell lung cancer patientsCell lung cancer patientsAdvanced NSCLC patientsCombination of erlotinibLung cancer patientsToxic regimenNSCLC patientsPretreatment serumCancer patientsWorse outcomesProteomic classifierBlinded mannerPatientsErlotinibBevacizumabVeriStratSurvivalTreatmentRegimenProgressionSerumClassification by Mass Spectrometry Can Accurately and Reliably Predict Outcome in Patients with Non-small Cell Lung Cancer Treated with Erlotinib-Containing Regimen
Salmon S, Chen H, Chen S, Herbst R, Tsao A, Tran H, Sandler A, Billheimer D, Shyr Y, Lee JW, Massion P, Brahmer J, Schiller J, Carbone D, Dang TP. Classification by Mass Spectrometry Can Accurately and Reliably Predict Outcome in Patients with Non-small Cell Lung Cancer Treated with Erlotinib-Containing Regimen. Journal Of Thoracic Oncology 2009, 4: 689-696. PMID: 19404214, PMCID: PMC3563261, DOI: 10.1097/jto.0b013e3181a526b3.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiomarkers, TumorCarcinoma, Non-Small-Cell LungCase-Control StudiesCohort StudiesErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalPleural Effusion, MalignantPrognosisQuinazolinesReproducibility of ResultsSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationSurvival RateTreatment OutcomeConceptsNon-small cell lung cancerCell lung cancerLung cancerRefractory non-small cell lung cancerPhase I/II studyUnivariate Cox proportional hazards modelProgression-free survival outcomesCox proportional hazards modelOutcomes of patientsCohort of patientsSelection of patientsVascular endothelial growth factorProportional hazards modelEndothelial growth factorReceptor kinase inhibitorEpidermal growth factor receptorGrowth factor receptorII studyOverall survivalPretreatment serumTreatment cohortsClinical outcomesSurvival outcomesEpidermal growth factor receptor kinase inhibitorsSuch therapy
2008
Bevacizumab and Erlotinib: A Promising New Approach to the Treatment of Advanced NSCLC
Herbst RS, Sandler A. Bevacizumab and Erlotinib: A Promising New Approach to the Treatment of Advanced NSCLC. The Oncologist 2008, 13: 1166-1176. PMID: 18997180, DOI: 10.1634/theoncologist.2008-0108.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerF. Hoffmann-La Roche LtdEpidermal growth factor receptorAdvanced non-small cell lung cancerTumor growthRandomized phase II trialRecombinant humanized monoclonal antibodyHuman epidermal growth factor receptorCombination of bevacizumabPhase II trialSelective tyrosine kinase inhibitorAdditional clinical benefitSecond-line alternativeCell lung cancerPotential predictive markerHumanized monoclonal antibodyVascular endothelial growth factorTyrosine kinase inhibitorsSouth San FranciscoEndothelial growth factorGrowth factor receptorAdvanced diseaseErlotinib monotherapyII trialProspective trialMolecular Characteristics of Bronchioloalveolar Carcinoma and Adenocarcinoma, Bronchioloalveolar Carcinoma Subtype, Predict Response to Erlotinib
Miller VA, Riely GJ, Zakowski MF, Li AR, Patel JD, Heelan RT, Kris MG, Sandler AB, Carbone DP, Tsao A, Herbst RS, Heller G, Ladanyi M, Pao W, Johnson DH. Molecular Characteristics of Bronchioloalveolar Carcinoma and Adenocarcinoma, Bronchioloalveolar Carcinoma Subtype, Predict Response to Erlotinib. Journal Of Clinical Oncology 2008, 26: 1472-1478. PMID: 18349398, DOI: 10.1200/jco.2007.13.0062.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma, Bronchiolo-AlveolarAdultAgedAged, 80 and overAntineoplastic AgentsBiomarkers, TumorDisease-Free SurvivalErbB ReceptorsErlotinib HydrochlorideFemaleHumansImmunohistochemistryLung NeoplasmsMaleMiddle AgedMutationProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsSuppressor of Cytokine Signaling ProteinsTreatment OutcomeConceptsProgression-free survivalBronchioloalveolar carcinomaResponse rateEGFR mutationsEGFR immunohistochemistryKRAS mutationsEpidermal growth factor receptor (EGFR) mutationsPrimary end pointEfficacy of erlotinibPhase II trialSubset of patientsCell lung cancerBAC subtypeOverall response rateKRAS mutation statusPure bronchioloalveolar carcinomaBronchioloalveolar carcinoma (BAC) subtypeMolecular characteristicsMedian OSII trialMedian survivalOverall survivalHistologic subtypeLung cancerUnivariate analysis
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 profileKRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer
Massarelli E, Varella-Garcia M, Tang X, Xavier AC, Ozburn NC, Liu DD, Bekele BN, Herbst RS, Wistuba II. KRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer. Clinical Cancer Research 2007, 13: 2890-2896. PMID: 17504988, DOI: 10.1158/1078-0432.ccr-06-3043.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungDisease ProgressionDrug Resistance, NeoplasmErbB ReceptorsErlotinib HydrochlorideFemaleGefitinibGene DosageHumansLung NeoplasmsMaleMiddle AgedMutationPrognosisProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsTreatment OutcomeConceptsEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsCell lung cancerKRAS mutationsTyrosine kinase inhibitorsEGFR-TKIEGFR copy numberEGFR mutationsLung cancerFavorable responseKinase inhibitorsShorter median timeArchival tissue specimensEGFR gene mutationsPanel of markersAdvanced NSCLCObjective responseProgressive diseaseSurvival benefitMedian timePoor responseSuch therapyDisease progressionPatients
2006
Angiogenesis inhibition in the treatment of lung cancer.
Vokes E, Herbst R, Sandler A. Angiogenesis inhibition in the treatment of lung cancer. Clinical Advances In Hematology And Oncology 2006, 4: 1-10; quiz 11-2. PMID: 17143257.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarboplatinCarcinoma, Non-Small-Cell LungClinical Trials, Phase III as TopicDisease-Free SurvivalErlotinib HydrochlorideHemorrhageHumansLung NeoplasmsNeovascularization, PathologicPaclitaxelProtein Kinase InhibitorsQuinazolinesRandomized Controlled Trials as TopicRisk FactorsSurvival RateVascular Endothelial Growth Factor AConceptsNon-small cell lung cancerVascular endothelial growth factorLung cancerAntiangiogenic therapyNon-squamous cell non-small cell lung cancerAnti-VEGF monoclonal antibody bevacizumabSmall molecule tyrosine kinase inhibitorsRandomized phase II studyRandomized phase III trialEpidermal growth factor receptor inhibitor erlotinibPhase II studyAddition of bevacizumabPhase III trialsSignificant survival benefitCell lung cancerSignificant clinical benefitMonoclonal antibody bevacizumabComprehensive treatment approachTyrosine kinase inhibitorsEndothelial growth factorImportant therapeutic targetOngoing studiesNSCLC settingBevacizumab treatmentII studyCombining Targeted Agents: Blocking the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways
Sandler A, Herbst R. Combining Targeted Agents: Blocking the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways. Clinical Cancer Research 2006, 12: 4421s-4425s. PMID: 16857821, DOI: 10.1158/1078-0432.ccr-06-0796.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Non-Small-Cell LungClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicDrug SynergismEpidermal Growth FactorErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleQuinazolinesVascular Endothelial Growth Factor AConceptsNon-small cell lung cancerPhase II doseStage IIIB/IV non-small cell lung cancerAdvanced non-small cell lung cancerPhase I/II studyEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsRandomized phase II trialVascular endothelial growth factor (VEGF) pathwaySelective epidermal growth factor receptor tyrosine kinase inhibitorEndothelial growth factor pathwayReceptor tyrosine kinase inhibitorsGrowth factorCommon adverse eventsMedian overall survivalPhase II trialPhase III trialsProgression-free survivalSafety of erlotinibCell lung cancerHumanized monoclonal antibodyVascular endothelial growth factorTyrosine kinase inhibitorsEndothelial growth factorGrowth factor pathways
2005
Mutations in the Epidermal Growth Factor Receptor and in KRAS Are Predictive and Prognostic Indicators in Patients With Non–Small-Cell Lung Cancer Treated With Chemotherapy Alone and in Combination With Erlotinib
Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, Ince WL, Jänne PA, Januario T, Johnson DH, Klein P, Miller VA, Ostland MA, Ramies DA, Sebisanovic D, Stinson JA, Zhang YR, Seshagiri S, Hillan KJ. Mutations in the Epidermal Growth Factor Receptor and in KRAS Are Predictive and Prognostic Indicators in Patients With Non–Small-Cell Lung Cancer Treated With Chemotherapy Alone and in Combination With Erlotinib. Journal Of Clinical Oncology 2005, 23: 5900-5909. PMID: 16043828, DOI: 10.1200/jco.2005.02.857.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCarcinoma, Non-Small-Cell LungCombined Modality TherapyDNA Mutational AnalysisErbB ReceptorsErlotinib HydrochlorideFemaleGenes, rasHumansLung NeoplasmsMaleMiddle AgedPaclitaxelPlacebosPredictive Value of TestsPrognosisQuinazolinesSurvival AnalysisTreatment OutcomeConceptsRetrospective subset analysisCell lung cancerEGFR mutationsKRAS mutationsLung cancerSubset analysisSingle-agent EGFR inhibitorsEpidermal growth factor receptor (EGFR) mutationsEGFR inhibitorsErlotinib-treated patientsFirst-line chemotherapyAdvanced NSCLC patientsChemotherapy-treated patientsPositive prognostic factorPoor clinical outcomeEGFR inhibitor treatmentImproved response ratesKRAS-mutant NSCLCKRAS exon 2Epidermal growth factor receptorGrowth factor receptorAdvanced NSCLCUntreated patientsNSCLC patientsPrognostic factorsTRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non–Small-Cell Lung Cancer
Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, Ramies D, Johnson DH, Miller VA. TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2005, 23: 5892-5899. PMID: 16043829, DOI: 10.1200/jco.2005.02.840.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCarcinoma, Non-Small-Cell LungDisease ProgressionErbB ReceptorsErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMiddle AgedPaclitaxelPlacebosProtein Kinase InhibitorsQuinazolinesSurvival AnalysisConceptsUntreated advanced NSCLCOverall survivalAdvanced NSCLCObjective responseLung cancerAdvanced non-small cell lung cancerEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsNon-small cell lung cancerEnd pointReceptor tyrosine kinase inhibitorsCycles of carboplatinGood performance statusImproved overall survivalOutcomes of patientsPrimary end pointSecondary end pointsPhase III trialsSingle-agent activityCell lung cancerDuration of responseTyrosine kinase inhibitorsAssessable patientsConcurrent carboplatinErlotinib armPhase I/II Trial Evaluating the Anti-Vascular Endothelial Growth Factor Monoclonal Antibody Bevacizumab in Combination With the HER-1/Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib for Patients With Recurrent Non–Small-Cell Lung Cancer
Herbst RS, Johnson DH, Mininberg E, Carbone DP, Henderson T, Kim ES, Blumenschein G, Lee JJ, Liu DD, Truong MT, Hong WK, Tran H, Tsao A, Xie D, Ramies DA, Mass R, Seshagiri S, Eberhard DA, Kelley SK, Sandler A. Phase I/II Trial Evaluating the Anti-Vascular Endothelial Growth Factor Monoclonal Antibody Bevacizumab in Combination With the HER-1/Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib for Patients With Recurrent Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2005, 23: 2544-2555. PMID: 15753462, DOI: 10.1200/jco.2005.02.477.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Non-Small-Cell LungDose-Response Relationship, DrugDrug InteractionsErlotinib HydrochlorideFemaleHumansInfusions, IntravenousLung NeoplasmsMaleMiddle AgedProtein Kinase InhibitorsQuinazolinesSurvival AnalysisTreatment OutcomeConceptsPhase II doseCell lung cancerLung cancerHumanized anti-vascular endothelial growth factor monoclonal antibodyVascular endothelial growth factor monoclonal antibody bevacizumabAnti-vascular endothelial growth factor monoclonal antibodyPhase I/II studyPhase I/II trialStage IIIB/IV NSCLCEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinibTyrosine kinase inhibitor erlotinibReceptor tyrosine kinase inhibitorsCommon adverse eventsMedian overall survivalProgression-free survivalDose-limiting toxicityFactor monoclonal antibodyMonoclonal antibody bevacizumabKinase inhibitor erlotinibTyrosine kinase inhibitorsAdenocarcinoma histologyModerate rashPrior chemotherapyErlotinib.
Herbst RS. Erlotinib. Clinical Advances In Hematology And Oncology 2005, 3: 125, 141. PMID: 16166980.Peer-Reviewed Original Research
2004
Review of epidermal growth factor receptor biology
Herbst RS. Review of epidermal growth factor receptor biology. International Journal Of Radiation Oncology • Biology • Physics 2004, 59: s21-s26. PMID: 15142631, DOI: 10.1016/j.ijrobp.2003.11.041.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorSignal transduction pathwaysSmall molecule inhibitorsTransduction pathwaysSubsequent activationReceptor tyrosine kinasesEpidermal growth factor receptor biologyTyrosine kinase phosphorylationEGFR inhibitorsTyrosine kinase receptorsIntracellular portionGrowth factor receptorCommon pharmacologic approachesEGFR activityEGFR activationExtracellular domainTyrosine kinaseKinase phosphorylationKinase receptorsCognate ligandsTransmembrane glycoproteinReceptor biologyErbB familyTumor cell linesCellular proliferation