2019
Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial
Herbst RS, Arkenau HT, Santana-Davila R, Calvo E, Paz-Ares L, Cassier PA, Bendell J, Penel N, Krebs MG, Martin-Liberal J, Isambert N, Soriano A, Wermke M, Cultrera J, Gao L, Widau RC, Mi G, Jin J, Ferry D, Fuchs CS, Petrylak DP, Chau I. Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial. The Lancet Oncology 2019, 20: 1109-1123. PMID: 31301962, DOI: 10.1016/s1470-2045(19)30458-9.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCarcinoma, Transitional CellDose-Response Relationship, DrugEsophageal NeoplasmsFemaleHumansLung NeoplasmsMaleMiddle AgedStomach NeoplasmsConceptsGastro-oesophageal junction adenocarcinomaTreatment-related adverse eventsCell lung cancerPhase 1a/b trialSerious adverse eventsDose-limiting toxicityAdverse eventsJunction adenocarcinomaUrothelial carcinomaLung cancerDay 1VEGF receptor 2Abdominal painPrevious therapyAdvanced gastricEastern Cooperative Oncology Group performance statusAntigen-specific T-cell migrationMore treatment-related adverse eventsTreatment-related serious adverse eventsAdditional dose-limiting toxicitiesCell lung cancer cohortGrade 3 abdominal painSingle-agent checkpoint inhibitorsB trialAntitumour activity
2017
Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases
Stevens LE, Cheung WKC, Adua SJ, Arnal-Estapé A, Zhao M, Liu Z, Brewer K, Herbst RS, Nguyen DX. Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases. Cancer Research 2017, 77: 1905-1917. PMID: 28196904, PMCID: PMC5468792, DOI: 10.1158/0008-5472.can-16-1978.Peer-Reviewed Original ResearchConceptsBrain metastatic nicheRisk of relapseDistant metastasisPoor prognosisLUAD subtypesLung tumorsLung adenocarcinomaLUAD cellsMetastatic outgrowthMetastatic nicheCancer ResCancer cellsECM-mediated signalingExtracellular matrix moleculesCell survivalMolecular signaturesDifferential expressionHMMRMatrix moleculesImportant mechanismCellsRelapseAdenocarcinomaPrognosisMetastasisWhole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up
Kadara H, Choi M, Zhang J, Parra ER, Rodriguez-Canales J, Gaffney SG, Zhao Z, Behrens C, Fujimoto J, Chow C, Yoo Y, Kalhor N, Moran C, Rimm D, Swisher S, Gibbons DL, Heymach J, Kaftan E, Townsend JP, Lynch TJ, Schlessinger J, Lee J, Lifton RP, Wistuba II, Herbst RS. Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up. Annals Of Oncology 2017, 28: 75-82. PMID: 27687306, PMCID: PMC5982809, DOI: 10.1093/annonc/mdw436.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalPoor recurrence-free survivalWhole-exome sequencingEarly-stage lung adenocarcinomaMutant lung adenocarcinomaLung adenocarcinomaImmune markersClinical outcomesExact testNatural killer cell infiltrationProportional hazards regression modelsGranzyme B levelsImmune marker analysisImmune profiling analysisPD-L1 expressionImmune-based therapiesTumoral PD-L1Hazards regression modelsKRAS mutant tumorsNormal lung tissuesMajority of deathsFisher's exact testHigh mutation burdenAnalysis of immunophenotypeRelevant molecular markers
2016
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohort
2015
Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities
Skoulidis F, Byers LA, Diao L, Papadimitrakopoulou VA, Tong P, Izzo J, Behrens C, Kadara H, Parra ER, Canales JR, Zhang J, Giri U, Gudikote J, Cortez MA, Yang C, Fan Y, Peyton M, Girard L, Coombes KR, Toniatti C, Heffernan TP, Choi M, Frampton GM, Miller V, Weinstein JN, Herbst RS, Wong KK, Zhang J, Sharma P, Mills GB, Hong WK, Minna JD, Allison JP, Futreal A, Wang J, Wistuba II, Heymach JV. Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities. Cancer Discovery 2015, 5: 860-877. PMID: 26069186, PMCID: PMC4527963, DOI: 10.1158/2159-8290.cd-14-1236.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesCell Line, TumorCluster AnalysisDNA-Binding ProteinsGene ExpressionGene Expression ProfilingGenetic VariationGenomicsHumansInflammationLung NeoplasmsMutationOxidative StressPrognosisProtein Serine-Threonine KinasesRas ProteinsSignal TransductionTranscription FactorsTumor Suppressor ProteinsConceptsKRAS-mutant lung adenocarcinomaCo-occurring genomic alterationsLung adenocarcinomaDistinct biologyTherapeutic vulnerabilitiesSTK11/LKB1Hsp90 inhibitor therapyRelapse-free survivalDrug sensitivity patternsGenomic alterationsCDKN2A/BKC tumorsInflammatory markersMucinous histologyImmune markersImmune profilePD-L1AdenocarcinomaSensitivity patternMajor subsetNKX2-1 transcription factorLow expressionTumorsGenetic alterationsEffector moleculesA Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress
Lee JW, Park HS, Park SA, Ryu SH, Meng W, Jürgensmeier JM, Kurie JM, Hong WK, Boyer JL, Herbst RS, Koo JS. A Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress. PLOS ONE 2015, 10: e0122628. PMID: 25897662, PMCID: PMC4405579, DOI: 10.1371/journal.pone.0122628.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAnilidesAntineoplastic AgentsApoptosis Regulatory ProteinsAutophagyAutophagy-Related Protein 7Bcl-2-Like Protein 11Cell Cycle CheckpointsCell Line, TumorCyclic AMP Response Element-Binding ProteinDrug Screening Assays, AntitumorEndoplasmic Reticulum StressHumansInhibitory Concentration 50Kaplan-Meier EstimateLung NeoplasmsMembrane ProteinsMolecular Docking SimulationOrganophosphatesPeptide FragmentsProportional Hazards ModelsProtein BindingProto-Oncogene ProteinsSialoglycoproteinsUbiquitin-Activating EnzymesConceptsLung cancerHuman lung cancer cell linesEndoplasmic reticulum (ER) stress markersLung cancer cell linesNovel therapeutic strategiesPotential therapeutic targetAnti-cancer effectsNovel small molecule inhibitorPotential therapeutic agentCyclic AMP response element binding proteinAccumulation of p62Response element-binding proteinEndoplasmic reticulum stressCancer cell linesCancer deathCommon subtypeCell cycle arrestLung adenocarcinomaNew therapiesTherapeutic strategiesSmall molecule inhibitorsTherapeutic targetElement-binding proteinStress markersTherapeutic agents
2014
Angiogenesis inhibition and lung-cancer therapy
Onn A, Bar J, Herbst RS. Angiogenesis inhibition and lung-cancer therapy. The Lancet Oncology 2014, 15: 124-125. PMID: 24480554, DOI: 10.1016/s1470-2045(14)70010-5.Peer-Reviewed Original Research
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 NSCLCIdentification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma
Cai G, Wong R, Chhieng D, Levy GH, Gettinger SN, Herbst RS, Puchalski JT, Homer RJ, Hui P. Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma. Cancer Cytopathology 2013, 121: 500-507. PMID: 23495083, DOI: 10.1002/cncy.21288.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAnaplastic Lymphoma KinaseBiomarkers, TumorBone NeoplasmsCytodiagnosisDNA, NeoplasmErbB ReceptorsFeasibility StudiesFemaleGene RearrangementHumansIn Situ Hybridization, FluorescenceLiver NeoplasmsLung NeoplasmsMaleMiddle AgedMutationNeoplasm Recurrence, LocalPrognosisProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsReal-Time Polymerase Chain ReactionReceptor Protein-Tyrosine KinasesSoft Tissue NeoplasmsYoung AdultConceptsALK gene rearrangementMetastatic lung adenocarcinomaEGFR mutationsKRAS mutationsMetastatic tumorsEpidermal growth factor receptorLung adenocarcinomaCytological specimensGene rearrangementsMolecular testsMolecular alterationsKirsten rat sarcoma viral oncogene homolog (KRAS) mutationsALK gene rearrangement analysisAnaplastic lymphoma kinase (ALK) gene rearrangementEGFR T790M mutationRat sarcoma viral oncogene homolog mutationsCases of lungT790M mutationImportant therapeutic implicationsFine needle aspiratesGene rearrangement analysisCell block materialGrowth factor receptorRecurrent lungRecurrent adenocarcinomaCXCR2 Expression in Tumor Cells Is a Poor Prognostic Factor and Promotes Invasion and Metastasis in Lung Adenocarcinoma
Saintigny P, Massarelli E, Lin S, Ahn YH, Chen Y, Goswami S, Erez B, O'Reilly MS, Liu D, Lee JJ, Zhang L, Ping Y, Behrens C, Soto L, Heymach JV, Kim ES, Herbst RS, Lippman SM, Wistuba II, Hong WK, Kurie JM, Koo JS. CXCR2 Expression in Tumor Cells Is a Poor Prognostic Factor and Promotes Invasion and Metastasis in Lung Adenocarcinoma. Cancer Research 2013, 73: 571-582. PMID: 23204236, PMCID: PMC3548940, DOI: 10.1158/0008-5472.can-12-0263.Peer-Reviewed Original ResearchConceptsGene expression profilesNon-small cell lung cancerKnockdown clonesNSCLC cell linesHuman NSCLC cell linesExpression profilesCell linesStable knockdown clonesLung adenocarcinomaLung adenocarcinoma cell linesTumor cellsRAS pathway activationCXCR2 expressionPoor prognosisLung cancer cellsOrthotopic syngeneic mouse modelAdenocarcinoma cell linePromotes InvasionExpression of CXCL5Role of CXCR2Poor prognostic factorCell lung cancerPromoter methylationSyngeneic mouse modelProtein expression
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 patientsMultitargeted Tyrosine Kinase Inhibitors in Unselected Patients With Advanced Non–Small-Cell Lung Cancer (NSCLC): Impressions From MONET (the Motesanib NSCLC Efficacy and Tolerability Study)
Morgensztern D, Herbst RS. Multitargeted Tyrosine Kinase Inhibitors in Unselected Patients With Advanced Non–Small-Cell Lung Cancer (NSCLC): Impressions From MONET (the Motesanib NSCLC Efficacy and Tolerability Study). Journal Of Clinical Oncology 2012, 30: 2805-2808. PMID: 22753916, DOI: 10.1200/jco.2012.42.7260.Peer-Reviewed Original ResearchTargeting Vascular Endothelial Growth Factor in Patients With Squamous Cell Lung Cancer
Koo PJ, Morgensztern D, Boyer JL, Herbst RS. Targeting Vascular Endothelial Growth Factor in Patients With Squamous Cell Lung Cancer. Journal Of Clinical Oncology 2012, 30: 1137-1139. PMID: 22355057, DOI: 10.1200/jco.2011.40.4053.Peer-Reviewed Original ResearchAdenocarcinomaAdenocarcinoma of LungAngiogenesis InhibitorsBiomarkers, TumorCarcinoma, Squamous CellGene Expression Regulation, NeoplasticHemorrhageHumansLung NeoplasmsNeoplasm StagingPredictive Value of TestsPrognosisReceptors, Vascular Endothelial Growth FactorSignal TransductionTreatment OutcomeVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3
2011
An Open-Label, Multicenter, Three-Stage, Phase II Study of S-1 in Combination with Cisplatin as First-Line Therapy for Patients with Advanced Non-small Cell Lung Cancer
Sandler A, Graham C, Baggstrom M, Herbst R, Zergebel C, Saito K, Jones D. An Open-Label, Multicenter, Three-Stage, Phase II Study of S-1 in Combination with Cisplatin as First-Line Therapy for Patients with Advanced Non-small Cell Lung Cancer. Journal Of Thoracic Oncology 2011, 6: 1400-1406. PMID: 21673602, DOI: 10.1097/jto.0b013e31820d7805.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Large CellCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCisplatinDrug CombinationsFemaleFollow-Up StudiesHumansLung NeoplasmsMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingOxonic AcidSurvival RateTegafurTreatment OutcomeConceptsNon-small cell lung cancerCell lung cancerLung cancerUnresectable non-small cell lung cancerAdvanced non-small cell lung cancerDay 1Response rateBest overall response rateMedian progression-free survivalCisplatin-based doubletsProtocol-specified criteriaDisease control rateObjective response ratePrimary end pointPhase II studyProgression-free survivalDeep vein thrombosisOverall response rateCisplatin regimenGastrointestinal toxicityOpen labelOral agentsAdverse eventsII studyLine therapyPhase II Trial of S-1 as Second-Line Therapy in Patients with Advanced Non-small Cell Lung Cancer
Govindan R, Morgensztern D, Kommor MD, Herbst RS, Schaefer P, Gandhi J, Saito K, Zergebel C, Schiller J. Phase II Trial of S-1 as Second-Line Therapy in Patients with Advanced Non-small Cell Lung Cancer. Journal Of Thoracic Oncology 2011, 6: 790-795. PMID: 21325974, DOI: 10.1097/jto.0b013e3182103b51.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntimetabolites, AntineoplasticCarcinoma, Large CellCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellDrug CombinationsFemaleFollow-Up StudiesHumansLung NeoplasmsMaleMiddle AgedNeoplasm StagingOxonic AcidPrognosisSalvage TherapySurvival RateTegafurConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerOverall response rateLung cancerAdvanced stage non-small cell lung cancerCommon treatment-related side effectsStage non-small cell lung cancerResponse rateMulticenter phase II studyTreatment-related side effectsDisease control rateLines of chemotherapyPhase II studyPrimary end pointSecond-line therapyPhase II trialProgression-free survivalNon-Asian populationsOral fluoropyrimidineOral SStable diseaseII trialII studyHistologic subtypeUpregulated 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
2010
A 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 ischemiaTreatment with HIF-1α Antagonist PX-478 Inhibits Progression and Spread of Orthotopic Human Small Cell Lung Cancer and Lung Adenocarcinoma in Mice
Jacoby JJ, Erez B, Korshunova MV, Williams RR, Furutani K, Takahashi O, Kirkpatrick L, Lippman SM, Powis G, O'Reilly MS, Herbst RS. Treatment with HIF-1α Antagonist PX-478 Inhibits Progression and Spread of Orthotopic Human Small Cell Lung Cancer and Lung Adenocarcinoma in Mice. Journal Of Thoracic Oncology 2010, 5: 940-949. PMID: 20512076, PMCID: PMC3782111, DOI: 10.1097/jto.0b013e3181dc211f.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsApoptosisBlotting, WesternCarcinoma, Non-Small-Cell LungDisease ProgressionHumansHypoxia-Inducible Factor 1, alpha SubunitImmunoenzyme TechniquesLung NeoplasmsLymphatic MetastasisMaleMiceMice, NudeMustard CompoundsPhenylpropionatesSmall Cell Lung CarcinomaSurvival RateTreatment OutcomeTumor Cells, CulturedConceptsLung tumor volumePX-478Tumor volumeLung cancerNSCLC modelsLung adenocarcinomaNon-small cell lung cancer xenograftsSmall cell lung cancer modelCell lung cancer xenograftsHuman small cell lung cancerSmall cell lung cancerCell lung cancer modelsPhase I clinical trialPX-478 treatmentAntitumor activityDaily oral treatmentMedian survival durationVehicle-treated groupCell lung cancerLung cancer xenograftsLung cancer patientsLung adenocarcinoma cell modelsLung cancer cell linesLung cancer modelOrthotopic mouse modelPhase 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
2008
Molecular 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