2017
The HGF/c-MET Pathway Is a Driver and Biomarker of VEGFR-inhibitor Resistance and Vascular Remodeling in Non–Small Cell Lung Cancer
Cascone T, Xu L, Lin HY, Liu W, Tran HT, Liu Y, Howells K, Haddad V, Hanrahan E, Nilsson MB, Cortez MA, Giri U, Kadara H, Saigal B, Park YY, Peng W, Lee JS, Ryan AJ, Jüergensmeier JM, Herbst RS, Wang J, Langley RR, Wistuba II, Lee JJ, Heymach JV. The HGF/c-MET Pathway Is a Driver and Biomarker of VEGFR-inhibitor Resistance and Vascular Remodeling in Non–Small Cell Lung Cancer. Clinical Cancer Research 2017, 23: 5489-5501. PMID: 28559461, PMCID: PMC5600821, DOI: 10.1158/1078-0432.ccr-16-3216.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Non-Small-Cell LungCell Line, TumorClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicDisease Models, AnimalDrug Resistance, NeoplasmGene Expression ProfilingHepatocyte Growth FactorHumansHypoxiaKaplan-Meier EstimateLung NeoplasmsMaleMiceMolecular Targeted TherapyMulticenter Studies as TopicNeovascularization, PathologicPrognosisProtein Kinase InhibitorsProto-Oncogene Proteins c-metReceptors, Vascular Endothelial Growth FactorSignal TransductionXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerHepatocyte growth factorC-MetHGF/c-Met pathwayHuman non-small cell lung cancerResistance of NSCLCAngiogenic factor levelsHGF plasma levelsCancer cellsTumor microvascular densityCell lung cancerEffect of therapyTortuous blood vesselsTumor vascular bedC-Met pathwayTyrosine kinase inhibitorsTumor-associated stromaClin Cancer ResHuman lung adenocarcinomaMurine xenograft modelVEGFR-TKIClinical outcomesLung cancerPlasma levelsMicrovascular density
2015
Lung-MAP—framework, overview, and design principles
Ferrarotto R, Redman MW, Gandara DR, Herbst RS, Papadimitrakopoulou VA. Lung-MAP—framework, overview, and design principles. Chinese Clinical Oncology 2015, 4: 36-36. PMID: 26408303, DOI: 10.3978/j.issn.2304-3865.2015.09.02.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicHigh-Throughput Screening AssaysHumansLung NeoplasmsMolecular Targeted TherapyNeoplasm MetastasisResearch DesignConceptsSquamous cell carcinomaLung-MAPClinical trialsMetastatic lung squamous cell carcinomaLung squamous cell carcinomaLung SCC patientsLimited therapeutic optionsEvidence of efficacyPoor patient outcomesClinical trial designDriver genetic alterationsEligible patientsSCC patientsPatients' qualityTreatment armsTherapeutic optionsCell carcinomaTherapy clinical trialsPatient outcomesTrial designMaster protocolsPatientsFDA approvalGenomic profilingPromising agentInnovative Clinical Trials: The LUNG‐MAP Study
Steuer C, Papadimitrakopoulou V, Herbst R, Redman M, Hirsch, Mack P, Ramalingam S, Gandara. Innovative Clinical Trials: The LUNG‐MAP Study. Clinical Pharmacology & Therapeutics 2015, 97: 488-491. PMID: 25676724, DOI: 10.1002/cpt.88.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBiomarkers, TumorCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicGenetic Predisposition to DiseaseGenomicsHumansLung NeoplasmsMolecular Targeted TherapyPhenotypePrecision MedicineResearch DesignSignal TransductionConceptsCell lung cancerSquamous cell carcinomaSquamous cell lung cancerCell carcinomaLung cancerTrial designNon-small cell lung cancerMetastatic squamous cell carcinomaSecond-line therapyProportion of patientsNew active drugsNovel trial designsDrug developmentWide molecular heterogeneityAdenocarcinoma histologyLine therapyTherapeutic optionsLung-MAPClinical trialsGroup trialsActive drugPatientsMaster protocolsCarcinomaCancer
2014
American Society of Clinical Oncology Perspective: Raising the Bar for Clinical Trials by Defining Clinically Meaningful Outcomes
Ellis LM, Bernstein DS, Voest EE, Berlin JD, Sargent D, Cortazar P, Garrett-Mayer E, Herbst RS, Lilenbaum RC, Sima C, Venook AP, Gonen M, Schilsky RL, Meropol NJ, Schnipper LE. American Society of Clinical Oncology Perspective: Raising the Bar for Clinical Trials by Defining Clinically Meaningful Outcomes. Journal Of Clinical Oncology 2014, 32: 1277-1280. PMID: 24638016, DOI: 10.1200/jco.2013.53.8009.Peer-Reviewed Original Research
2012
Effect of KRAS Oncogene Substitutions on Protein Behavior: Implications for Signaling and Clinical Outcome
Ihle NT, Byers LA, Kim ES, Saintigny P, Lee JJ, Blumenschein GR, Tsao A, Liu S, Larsen JE, Wang J, Diao L, Coombes KR, Chen L, Zhang S, Abdelmelek MF, Tang X, Papadimitrakopoulou V, Minna JD, Lippman SM, Hong WK, Herbst RS, Wistuba II, Heymach JV, Powis G. Effect of KRAS Oncogene Substitutions on Protein Behavior: Implications for Signaling and Clinical Outcome. Journal Of The National Cancer Institute 2012, 104: 228-239. PMID: 22247021, PMCID: PMC3274509, DOI: 10.1093/jnci/djr523.Peer-Reviewed Original ResearchMeSH KeywordsAspartic AcidCarcinoma, Non-Small-Cell LungCell Line, TumorClinical Trials, Phase II as TopicCysteineDisease-Free SurvivalGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, rasGenetic VectorsGlycineHumansImmunoblottingImmunoprecipitationKaplan-Meier EstimateLentivirusLung NeoplasmsMicroarray AnalysisMolecular Targeted TherapyMutationProto-Oncogene Proteins c-aktRandomized Controlled Trials as TopicSignal TransductionTOR Serine-Threonine KinasesTreatment OutcomeValineConceptsNon-small cell lung cancerKirsten rat sarcoma viral oncogene homologProgression-free survivalNSCLC cell linesWild-type KrasMutant KrasRefractory non-small cell lung cancerWorse progression-free survivalRat sarcoma viral oncogene homologRas2 Kirsten rat sarcoma viral oncogene homologSarcoma viral oncogene homologKaplan-Meier curvesCell lung cancerReverse-phase protein array studiesKRas proteinsHuman bronchial epithelial cellsCancer cell growthPatient tumor samplesCell linesImmortalized human bronchial epithelial cellsBronchial epithelial cellsProtein array studiesTumor gene expressionEvaluable patientsClinical outcomes
2009
Baseline 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 subjectsThe changing face of Phase 1 cancer clinical trials
Craft BS, Kurzrock R, Lei X, Herbst R, Lippman S, Fu S, Karp DD. The changing face of Phase 1 cancer clinical trials. Cancer 2009, 115: 1592-1597. PMID: 19165808, PMCID: PMC2668727, DOI: 10.1002/cncr.24171.Peer-Reviewed Original ResearchMeSH KeywordsBiomedical ResearchClinical ProtocolsClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicNeoplasmsPatient SelectionPhysical ExaminationResearch DesignUnited StatesConceptsPhase 2 trialEarly phase clinical trialsPhase 1 studyPhase 1 trialClinical trialsVital sign determinationsCancer clinical trialsPhysical examinationEarly phase cancer clinical trialsWeeks of protocolPhase 2 studyPhase 1 cancer clinical trialsNew drug studyStudy requirementsPhase 1Pharmacokinetic samplingMore patientsMedical oncologyOncology communityLaboratory testsSuch trialsDrug studiesTrialsPhase 1 programElectrocardiogram
2006
Combining 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
2003
Gefitinib: current and future status in cancer therapy.
Herbst RS, Kies MS. Gefitinib: current and future status in cancer therapy. Clinical Advances In Hematology And Oncology 2003, 1: 466-72. PMID: 16258434.Peer-Reviewed Original ResearchMeSH KeywordsClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicDrug EvaluationErbB ReceptorsGefitinibHumansNeoplasmsQuinazolinesSignal TransductionConceptsEpidermal growth factor receptorTumor growthEGFR tyrosine kinase inhibitorsCurrent clinical development statusOngoing clinical trialsCombination of gefitinibClinical development statusCancer cell growthHost-dependent processesGrowth factor receptorHormonal therapyStandard chemotherapyBiologic agentsDisease recurrenceCell lungSolid malignanciesClinical trialsTumor cell functionsViable drug targetNovel agentsPreclinical studiesClinical developmentTumor typesGefitinibKinase inhibitorsDose-comparative monotherapy trials of ZD1839 in previously treated non–small cell lung cancer patients
Herbst RS. Dose-comparative monotherapy trials of ZD1839 in previously treated non–small cell lung cancer patients. Seminars In Oncology 2003, 30: 30-38. PMID: 12644982, DOI: 10.1053/sonc.2003.50030.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungClinical Trials, Phase II as TopicEnzyme InhibitorsErbB ReceptorsGefitinibHumansLung NeoplasmsProtein-Tyrosine KinasesQuinazolinesRandomized Controlled Trials as TopicConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerSymptom improvement rateTumor response rateDay groupSolid tumorsChemotherapy regimensIDEAL-2Ideal 1Lung cancerClinical trialsStage IIIResponse rateNon-small cell lung cancer patientsEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsAdvanced unresectable stage IIIMedian progression-free survivalObjective tumor response rateCell lung cancer patientsImprovement rateSelective epidermal growth factor receptor tyrosine kinase inhibitorReceptor tyrosine kinase inhibitorsPhase I clinical trialIressa Dose Evaluation
2002
ZD1839: targeting the epidermal growth factor receptor in cancer therapy
Herbst RS. ZD1839: targeting the epidermal growth factor receptor in cancer therapy. Expert Opinion On Investigational Drugs 2002, 11: 837-849. PMID: 12036427, DOI: 10.1517/13543784.11.6.837.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerEpidermal growth factor receptorCell lung cancerGrowth factor receptorFactor receptorLung cancerSmall-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitorTumor typesEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsAntitumour activityReceptor tyrosine kinase inhibitorsMeaningful antitumour activityAcceptable tolerability profilePaclitaxel/carboplatinPhase II studyThird-line treatmentFirst-line treatmentPhase III trialsGemcitabine/cisplatinClinical trial programPromising clinical activityCancer cell growthHost-dependent processesAdvanced disease