2018
Should chemotherapy plus immune checkpoint inhibition be the standard front‐line therapy for patients with metastatic non–small cell lung cancer?
Goldberg SB, Herbst RS. Should chemotherapy plus immune checkpoint inhibition be the standard front‐line therapy for patients with metastatic non–small cell lung cancer? Cancer 2018, 124: 4592-4596. PMID: 30383887, PMCID: PMC6443243, DOI: 10.1002/cncr.31681.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerLung cancerNonsquamous non-small cell lung cancerAdvanced non-small cell lung cancerMetastatic non-small cell lung cancerCell death protein 1 (PD-1) inhibitorsStandard front-line therapyFirst-line settingImmune checkpoint inhibitionFront-line therapyNew treatment optionsProtein 1 inhibitorCheckpoint inhibitionTumor histologyTreatment optionsRecent trialsPatientsCancerChemotherapyTherapyHistologyMajor advancementsTrials
2013
Phase II Trial of Carboplatin, Paclitaxel, Cetuximab, and Bevacizumab Followed by Cetuximab and Bevacizumab in Advanced Nonsquamous Non–Small-Cell Lung Cancer: SWOG S0536
Kim ES, Moon J, Herbst RS, Redman MW, Dakhil SR, Velasco MR, Hirsch FR, Mack PC, Kelly K, Heymach JV, Gandara DR. Phase II Trial of Carboplatin, Paclitaxel, Cetuximab, and Bevacizumab Followed by Cetuximab and Bevacizumab in Advanced Nonsquamous Non–Small-Cell Lung Cancer: SWOG S0536. Journal Of Thoracic Oncology 2013, 8: 1519-1528. PMID: 24189513, PMCID: PMC4072123, DOI: 10.1097/jto.0000000000000009.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarboplatinCarcinoma, Non-Small-Cell LungCetuximabFeasibility StudiesFemaleFollow-Up StudiesHumansLung NeoplasmsMaleMiddle AgedNeoplasm StagingPaclitaxelPrognosisSurvival RateConceptsPhase II trialProgression-free survivalII trialPrimary endpointOverall survivalLung cancerAdvanced nonsquamous non-small cell lung cancerNonsquamous non-small cell lung cancerResponse rateNon-small cell lung cancerMedian progression-free survivalOverall disease control rateCycles of carboplatinPlatinum-based doubletsTreatment-related deathsChemotherapy-naive patientsDisease control rateMedian overall survivalCombination of carboplatinCell lung cancerHigher hemorrhageMaintenance cetuximabStable diseaseAdvanced NSCLCNonsquamous NSCLC
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 erlotinibUpregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor–resistant human lung adenocarcinoma
Cascone T, Herynk MH, Xu L, Du Z, Kadara H, Nilsson MB, Oborn CJ, Park YY, Erez B, Jacoby JJ, Lee JS, Lin HY, Ciardiello F, Herbst RS, Langley RR, Heymach JV. Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor–resistant human lung adenocarcinoma. Journal Of Clinical Investigation 2011, 121: 1313-1328. PMID: 21436589, PMCID: PMC3070607, DOI: 10.1172/jci42405.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAngiogenesis InhibitorsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedApoptosisBevacizumabCell Line, TumorDrug Resistance, NeoplasmErbB ReceptorsGene Expression ProfilingHumansLung NeoplasmsMaleMiceMice, NudeNeovascularization, PathologicRNA, MessengerRNA, NeoplasmStromal CellsUp-RegulationVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsMouse xenograft modelHuman lung adenocarcinomaTumor cellsPrimary resistanceLung adenocarcinomaXenograft modelFGFR pathwayProgression-free survivalVEGF inhibitor bevacizumabEndothelium of tumorsInhibitors of angiogenesisCombination regimensTreatment of cancerVEGF inhibitorsPericyte coverageAntiangiogenic therapyVascular remodelingAngiogenesis inhibitorsTherapeutic efficacyTumor growthStromal pathwaysClinical useEGFRAcquired ResistanceEGFR pathway
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 mannerPatientsErlotinibBevacizumabVeriStratSurvivalTreatmentRegimenProgressionSerumSafety, Pharmacokinetics, and Antitumor Activity of AMG 386, a Selective Angiopoietin Inhibitor, in Adult Patients With Advanced Solid Tumors
Herbst RS, Hong D, Chap L, Kurzrock R, Jackson E, Silverman JM, Rasmussen E, Sun YN, Zhong D, Hwang YC, Evelhoch JL, Oliner JD, Le N, Rosen LS. Safety, Pharmacokinetics, and Antitumor Activity of AMG 386, a Selective Angiopoietin Inhibitor, in Adult Patients With Advanced Solid Tumors. Journal Of Clinical Oncology 2009, 27: 3557-3565. PMID: 19546406, DOI: 10.1200/jco.2008.19.6683.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAngiopoietinsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntimetabolites, AntineoplasticBevacizumabDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFatigueFemaleHumansInfusions, IntravenousMaleMaximum Tolerated DoseMiddle AgedNeoplasm StagingNeoplasmsTreatment OutcomeConceptsAMG 386Advanced solid tumorsPartial responseAntitumor activitySolid tumorsElimination half-life valuesPatients 48 hoursMaximum-tolerated doseTreatment-related toxicityDose-limiting toxicityRefractory ovarian cancerWeeks of treatmentPeptide-Fc fusion proteinVolume transfer constantAngiopoietin inhibitorsCommon toxicitiesStable diseasePeripheral edemaAdult patientsClinical sequelaeMethods PatientsWeekly dosesTumor burdenRespiratory arrestSafety profileClassification 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 trialBevacizumab/Chemotherapy in Non–Small-Cell Lung Cancer: Looking for A Few Good Men?
Herbst RS. Bevacizumab/Chemotherapy in Non–Small-Cell Lung Cancer: Looking for A Few Good Men? Clinical Lung Cancer 2008, 9: 75-76. PMID: 18501092, DOI: 10.3816/clc.2008.n.011.Peer-Reviewed Original Research
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 profile
2006
Toxicities of Antiangiogenic Therapy in Non–Small-Cell Lung Cancer
Herbst RS. Toxicities of Antiangiogenic Therapy in Non–Small-Cell Lung Cancer. Clinical Lung Cancer 2006, 8: s23-s30. PMID: 17239287, DOI: 10.3816/clc.2006.s.010.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBenzenesulfonatesBevacizumabCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellHumansIndolesLung NeoplasmsNiacinamidePhenylurea CompoundsPiperidinesPyridinesPyrrolesQuinazolinesSorafenibSunitinibVascular Endothelial Growth FactorsConceptsAnti-VEGF antibodyCell lung cancerVascular endothelial growth factorAntiangiogenic agentsOverall survivalLung cancerPhase III pivotal trialsClass-effect toxicitiesFirst-line chemotherapyAdverse event profileSquamous cell histologyChemotherapy-associated toxicityVEGFR tyrosine kinaseTyrosine kinase inhibitorsEndothelial growth factorMetastatic NSCLCThromboembolic eventsCell histologyPivotal trialsEvent profileRisk factorsVEGF receptor activityAntiangiogenic therapySmall molecule inhibitorsTumor typesAngiogenesis 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
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
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 chemotherapy
2004
Anti-Vascular Endothelial Growth Factor Monoclonals in Non-Small Cell Lung Cancer
Sandler AB, Johnson DH, Herbst RS. Anti-Vascular Endothelial Growth Factor Monoclonals in Non-Small Cell Lung Cancer. Clinical Cancer Research 2004, 10: 4258s-4262s. PMID: 15217970, DOI: 10.1158/1078-0432.ccr-040023.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerMetastatic non-small cell lung cancerCarboplatin/paclitaxel chemotherapyCell lung cancerVascular endothelial growth factorEndothelial growth factorPaclitaxel chemotherapyLung cancerAdvanced metastatic non-small cell lung cancerStandard carboplatin/paclitaxel chemotherapyPhase I/II studyRecent phase II trialGrowth factorCurrent chemotherapy regimensEastern Cooperative GroupNeo-adjuvant studyNon-squamous histologyRole of bevacizumabNausea/vomitingAddition of bevacizumabPhase II trialPhase III studyTyrosine kinase inhibitor agentsSquamous cell histologySubset of patientsNon-Small Cell Lung Cancer and Antiangiogenic Therapy: What Can Be Expected of Bevacizumab?
Herbst RS, Sandler AB. Non-Small Cell Lung Cancer and Antiangiogenic Therapy: What Can Be Expected of Bevacizumab? The Oncologist 2004, 9: 19-26. PMID: 15178812, DOI: 10.1634/theoncologist.9-suppl_1-19.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerVascular endothelial growth factorCarboplatin/paclitaxel chemotherapyCell lung cancerPaclitaxel chemotherapyLung cancerAdvanced metastatic non-small cell lung cancerMetastatic non-small cell lung cancerStandard carboplatin/paclitaxel chemotherapyResponse rateRecent phase II trialCurrent chemotherapy regimensNausea/vomitingAddition of bevacizumabPhase II trialSquamous cell histologySubset of patientsNegative prognostic significancePossible risk factorsGreater response rateMean survival timeEndothelial growth factorMain safety concernsAdjuvant settingNonsquamous histologyRandomized Phase II Trial Comparing Bevacizumab Plus Carboplatin and Paclitaxel With Carboplatin and Paclitaxel Alone in Previously Untreated Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized Phase II Trial Comparing Bevacizumab Plus Carboplatin and Paclitaxel With Carboplatin and Paclitaxel Alone in Previously Untreated Locally Advanced or Metastatic Non-Small-Cell Lung Cancer. Journal Of Clinical Oncology 2004, 22: 2184-2191. PMID: 15169807, DOI: 10.1200/jco.2004.11.022.Peer-Reviewed Original ResearchConceptsCell lung cancerSingle-agent bevacizumabLung cancerMajor hemoptysisCell histologyControl armResponse ratePrimary efficacy end pointNonsquamous cell histologyProminent adverse eventSafety of bevacizumabEfficacy end pointDistinct clinical patternsPhase II trialSquamous cell histologyLonger median timeHigh response rateMajor blood vesselsPreviously UntreatedStable diseaseII trialAdverse eventsControl patientsClinical patternMedian time