2017
Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers
Nilsson MB, Sun H, Diao L, Tong P, Liu D, Li L, Fan Y, Poteete A, Lim SO, Howells K, Haddad V, Gomez D, Tran H, Pena GA, Sequist LV, Yang JC, Wang J, Kim ES, Herbst R, Lee JJ, Hong WK, Wistuba I, Hung MC, Sood AK, Heymach JV. Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers. Science Translational Medicine 2017, 9 PMID: 29118262, PMCID: PMC5870120, DOI: 10.1126/scitranslmed.aao4307.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AntagonistsAfatinibAMP-Activated Protein Kinase KinasesCarcinoma, Non-Small-Cell LungCell Line, TumorCyclic AMP Response Element-Binding ProteinDrug Resistance, NeoplasmEpinephrineErbB ReceptorsHumansInterleukin-6Lung NeoplasmsMutationNorepinephrineProtein Kinase CProtein Kinase InhibitorsProtein Serine-Threonine KinasesQuinazolinesReceptors, Adrenergic, betaSignal TransductionXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerEGFR inhibitor resistanceΒ-blockersInhibitor resistanceStress hormonesLiver kinase B1Epidermal growth factor receptor tyrosine kinase inhibitor resistanceLower IL-6 concentrationsΒ-blocker useIL-6 concentrationsIL-6 inhibitionCell lung cancerTyrosine kinase inhibitor resistanceEGFR-TKI resistanceInterleukin-6 expressionKinase inhibitor resistanceChronic stress hormonesNSCLC patientsEGFR-TKIIL-6Lung cancerAR activationWorse outcomesNSCLC cellsTKI resistance
2016
KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib
Nilsson MB, Giri U, Gudikote J, Tang X, Lu W, Tran H, Fan Y, Koo A, Diao L, Tong P, Wang J, Herbst R, Johnson BE, Ryan A, Webster A, Rowe P, Wistuba II, Heymach JV. KDR Amplification Is Associated with VEGF-Induced Activation of the mTOR and Invasion Pathways but does not Predict Clinical Benefit to the VEGFR TKI Vandetanib. Clinical Cancer Research 2016, 22: 1940-1950. PMID: 26578684, PMCID: PMC4834253, DOI: 10.1158/1078-0432.ccr-15-1994.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungCell Line, TumorCell MovementCell ProliferationHumansHypoxia-Inducible Factor 1, alpha SubunitLung NeoplasmsP38 Mitogen-Activated Protein KinasesPiperidinesProtein Kinase InhibitorsProto-Oncogene Proteins c-metQuinazolinesSignal TransductionTOR Serine-Threonine KinasesTreatment OutcomeVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsNon-small cell lung cancerTyrosine kinase inhibitorsVEGFR tyrosine kinase inhibitorsNSCLC cell linesZODIAC studyClinical benefitLung cancerPlatinum-refractory non-small cell lung cancerAdvanced non-small cell lung cancerImproved progression-free survivalDifferent lung cancersObjective response rateProgression-free survivalVEGF pathway inhibitorsCell lung cancerArchival tumor samplesCell linesActivation of mTORVandetanib armOverall survivalNSCLC modelsNSCLC cellsPreclinical studiesPatientsVEGFR inhibition
2015
EGFR tyrosine kinase inhibitors in squamous cell lung cancer
Hirsch FR, Herbst RS, Gandara DR. EGFR tyrosine kinase inhibitors in squamous cell lung cancer. The Lancet Oncology 2015, 16: 872-873. PMID: 26156654, DOI: 10.1016/s1470-2045(15)00126-6.Peer-Reviewed Original ResearchA retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies
Platt A, Morten J, Ji Q, Elvin P, Womack C, Su X, Donald E, Gray N, Read J, Bigley G, Blockley L, Cresswell C, Dale A, Davies A, Zhang T, Fan S, Fu H, Gladwin A, Harrod G, Stevens J, Williams V, Ye Q, Zheng L, de Boer R, Herbst RS, Lee JS, Vasselli J. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies. BMC Cancer 2015, 15: 171. PMID: 25881079, PMCID: PMC4412099, DOI: 10.1186/s12885-015-1146-8.Peer-Reviewed Original ResearchConceptsGene copy number gainCopy number gainsRET rearrangementsTumor samplesComparator armVandetanib treatmentNumber gainRandomized phase III studyPhase III clinical trialsCell lung cancer trialsObjective response ratePhase III studyLung cancer trialsRET protein expressionNSCLC subpopulationVandetanib armRadiologic evidenceIII studyNSCLC patientsObjective responseTumor shrinkageComparator drugsCancer trialsClinical trialsRetrospective analysis
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 ResearchEGFR 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 samplesVandetanib and Indwelling Pleural Catheter for Non–Small-Cell Lung Cancer With Recurrent Malignant Pleural Effusion
Massarelli E, Onn A, Marom EM, Alden CM, Liu DD, Tran HT, Mino B, Wistuba II, Faiz SA, Bashoura L, Eapen GA, Morice RC, Lee J, Hong WK, Herbst RS, Jimenez CA. Vandetanib and Indwelling Pleural Catheter for Non–Small-Cell Lung Cancer With Recurrent Malignant Pleural Effusion. Clinical Lung Cancer 2014, 15: 379-386. PMID: 24913066, PMCID: PMC4160385, DOI: 10.1016/j.cllc.2014.04.002.Peer-Reviewed Original ResearchConceptsRecurrent malignant pleural effusionCell lung cancer patientsMalignant pleural effusionLung cancer patientsCell lung cancerPleural effusionCancer patientsMedian timeCatheter placementLung cancerEastern Cooperative Oncology Group performance statusPoor overall median survivalEnd pointSingle-arm phase II clinical trialPhase II clinical trialIndwelling pleural catheterOverall median survivalPrimary end pointSecondary end pointsDaily oral doseWeeks of treatmentPleural fluid cytologyVEGF receptor inhibitorPleural fluid cytokinesEligible patients
2013
Clinical and Biomarker Outcomes of the Phase II Vandetanib Study from the BATTLE Trial
Tsao AS, Liu S, Lee JJ, Alden CM, Blumenschein GR, Herbst R, Davis SE, Kim E, Lippman S, Heymach J, Tran H, Tang X, Wistuba I, Hong WK. Clinical and Biomarker Outcomes of the Phase II Vandetanib Study from the BATTLE Trial. Journal Of Thoracic Oncology 2013, 8: 658-661. PMID: 23584298, PMCID: PMC5118909, DOI: 10.1097/jto.0b013e31828d08ae.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAgedAntineoplastic AgentsBiomarkers, TumorCarcinoma, Non-Small-Cell LungDisease-Free SurvivalFemaleGene AmplificationGenes, erbB-1HumansInterleukin-9Kaplan-Meier EstimateLipocalin-2LipocalinsLung NeoplasmsMaleMiddle AgedMutationPiperidinesProportional Hazards ModelsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsTNF-Related Apoptosis-Inducing LigandConceptsDisease control rateWorse OSShorter PFSControl rateMutation patientsDual epidermal growth factor receptorVascular endothelial growth factor receptor inhibitionLung Cancer Elimination (BATTLE) trialNeutrophil gelatinase-associated lipocalinCell lung cancer patientsGrowth factor receptor inhibitionPhase II trialGelatinase-associated lipocalinLung cancer patientsTumor core biopsiesSerum biomarker analysisEGFR mutation patientsEpidermal growth factor receptorEGFR gene amplificationApoptosis-inducing ligandGrowth factor receptorMedian PFSOS benefitEpidermal growth factor receptor tyrosine kinaseII trialPhase 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 EGFRCaspase-Independent Cell Death Is Involved in the Negative Effect of EGF Receptor Inhibitors on Cisplatin in Non–Small Cell Lung Cancer Cells
Yamaguchi H, Hsu JL, Chen CT, Wang YN, Hsu MC, Chang SS, Du Y, Ko HW, Herbst R, Hung MC. Caspase-Independent Cell Death Is Involved in the Negative Effect of EGF Receptor Inhibitors on Cisplatin in Non–Small Cell Lung Cancer Cells. Clinical Cancer Research 2013, 19: 845-854. PMID: 23344263, PMCID: PMC3703145, DOI: 10.1158/1078-0432.ccr-12-2621.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCaspasesCell DeathCell Line, TumorCisplatinDrug Resistance, NeoplasmEpidermal Growth FactorErbB ReceptorsForkhead Box Protein O3Forkhead Transcription FactorsGefitinibHumansProtein Kinase InhibitorsQuinazolinesSignal TransductionConceptsCaspase-independent cell deathTyrosine kinase inhibitorsSuberoylanilide hydroxamic acidReactive oxygen speciesLung cancerCell deathEGFR cellsEffects of TKIsNon-small cell lung cancer cellsCaspase-dependent apoptotic cell deathCisplatin-induced reactive oxygen speciesReceptor tyrosine kinase inhibitorsInducer of ROSCell lung cancer cellsPlatinum-based chemotherapyEGF receptor tyrosine kinase inhibitorMultiple clinical trialsEfficacy of chemotherapyEfficacy of cisplatinEffect of cisplatinLung cancer cellsApoptotic cell deathWild-type EGFREGF receptor inhibitorClinical trials
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 patientsCombined MEK and VEGFR Inhibition in Orthotopic Human Lung Cancer Models Results in Enhanced Inhibition of Tumor Angiogenesis, Growth, and Metastasis
Takahashi O, Komaki R, Smith PD, Jürgensmeier JM, Ryan A, Bekele BN, Wistuba II, Jacoby JJ, Korshunova MV, Biernacka A, Erez B, Hosho K, Herbst RS, O'Reilly MS. Combined MEK and VEGFR Inhibition in Orthotopic Human Lung Cancer Models Results in Enhanced Inhibition of Tumor Angiogenesis, Growth, and Metastasis. Clinical Cancer Research 2012, 18: 1641-1654. PMID: 22275507, PMCID: PMC3306446, DOI: 10.1158/1078-0432.ccr-11-2324.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationDisease ProgressionHumansLung NeoplasmsMaleMiceMice, NudeMitogen-Activated Protein KinasesMolecular Targeted TherapyNeovascularization, PathologicPaclitaxelProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsReceptors, Vascular Endothelial Growth FactorXenograft Model Antitumor AssaysConceptsSignal-regulated kinase kinaseTumor cell proliferationCell proliferationReceptor tyrosine kinasesKinase kinaseAvailable MEK1/2 inhibitorHuman NSCLC cellsTyrosine kinaseVEGF receptor tyrosine kinasesERK phosphorylationNCI-H441MEK1/2 inhibitorApoptotic effectsAdjacent normal tissuesKinaseNSCLC cellsMEK inhibitionAntiangiogenic effectsSignalingOrthotopic human lung cancer modelAvailable potent inhibitorLung tumor growthPotent inhibitorTumor angiogenesisSelumetinib
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 therapyVandetanib 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 receptorA 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 therapyBaseline Vascular Endothelial Growth Factor Concentration as a Potential Predictive Marker of Benefit from Vandetanib in Non–Small Cell Lung Cancer
Hanrahan EO, Ryan AJ, Mann H, Kennedy SJ, Langmuir P, Natale RB, Herbst RS, Johnson BE, Heymach JV. Baseline Vascular Endothelial Growth Factor Concentration as a Potential Predictive Marker of Benefit from Vandetanib in Non–Small Cell Lung Cancer. Clinical Cancer Research 2009, 15: 3600-3609. PMID: 19447868, DOI: 10.1158/1078-0432.ccr-08-2568.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Non-Small-Cell LungClinical Trials, Phase II as TopicEnzyme-Linked Immunosorbent AssayHumansKaplan-Meier EstimateLung NeoplasmsMeta-Analysis as TopicPiperidinesPredictive Value of TestsQuinazolinesRandomized Controlled Trials as TopicReceptors, Vascular Endothelial Growth FactorTreatment OutcomeVascular Endothelial Growth Factor AConceptsNon-small cell lung cancerProgression-free survivalCell lung cancerAdvanced non-small cell lung cancerVandetanib monotherapyLung cancerDisease progressionVEGF levelsVEGF valuesSimilar riskRandomized phase II studyVascular endothelial growth factor concentrationsExploratory retrospective analysisPhase II studyBaseline VEGF levelsPotential predictive markerLower VEGF levelsGrowth factor concentrationsBaseline VEGFCarboplatin-paclitaxelPFS advantageII studyPredictive markerRetrospective analysisHealthy subjects