2020
PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice
Eguren-Santamaria I, Sanmamed MF, Goldberg SB, Kluger HM, Idoate MA, Lu B, Corral J, Schalper KA, Herbst RS, Gil-Bazo I. PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice. Clinical Cancer Research 2020, 26: 4186-4197. PMID: 32354698, DOI: 10.1158/1078-0432.ccr-20-0798.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsAnti-PD-1/PD-L1 antibodiesAdvanced non-small cell lung cancerNSCLC brain metastasesBrain metastasesPD-L1 antibodiesAnti-PD-1/PD-L1 agentsPD-1/PD-L1 blockersActive central nervous system (CNS) involvementHigh PD-L1 expressionAnti-PD-1/PD-L1 drugsCentral nervous system involvementPivotal phase III trialsActive brain metastasesCNS response ratesPD-L1 agentsPD-L1 blockersSystemic therapy combinationsNervous system involvementPD-L1 expressionPhase III trialsSubset of patientsCell lung cancerPD-L1 drugsPembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial
Goldberg SB, Schalper KA, Gettinger SN, Mahajan A, Herbst RS, Chiang AC, Lilenbaum R, Wilson FH, Omay SB, Yu JB, Jilaveanu L, Tran T, Pavlik K, Rowen E, Gerrish H, Komlo A, Gupta R, Wyatt H, Ribeiro M, Kluger Y, Zhou G, Wei W, Chiang VL, Kluger HM. Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2020, 21: 655-663. PMID: 32251621, PMCID: PMC7380514, DOI: 10.1016/s1470-2045(20)30111-x.Peer-Reviewed Original ResearchConceptsBrain metastasis responseYale Cancer CenterPD-L1 expressionPhase 2 trialUntreated brain metastasesBrain metastasesAdrenal insufficiencyAdverse eventsMetastasis responseCNS diseaseCancer CenterCohort 2Cohort 1Eastern Cooperative Oncology Group performance statusTreatment-related serious adverse eventsModified Response Evaluation CriteriaStage IV NSCLCTreatment-related deathsAcute kidney injuryPD-1 blockadeSerious adverse eventsSolid Tumors criteriaPhase 2 studyProportion of patientsResponse Evaluation Criteria
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 advancementsTrialsSafety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study
Horn L, Gettinger SN, Gordon MS, Herbst RS, Gandhi L, Felip E, Sequist LV, Spigel DR, Antonia SJ, Balmanoukian A, Cassier PA, Liu B, Kowanetz M, O'Hear C, Fassò M, Grossman W, Sandler A, Soria JC. Safety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study. European Journal Of Cancer 2018, 101: 201-209. PMID: 30077125, DOI: 10.1016/j.ejca.2018.06.031.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsBaseline PD-L1 expressionObjective response ratePD-L1 expressionPD-L1Immune cellsGrade treatment-related adverse eventsSurvival rateCell lung cancer cohortLong-term clinical benefitTumor-infiltrating immune cellsTumor cellsPhase IPrevious systemic therapySingle-agent atezolizumabCell lung cancerExploratory subgroup analysisLung cancer cohortAtezolizumab monotherapyAdverse eventsDurable responsesMedian durationSystemic therapyAnticancer immunityPD-1
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 ResearchConceptsSquamous 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 agent
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 EGFRCXCR2 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 expressionAn Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance
Byers LA, Diao L, Wang J, Saintigny P, Girard L, Peyton M, Shen L, Fan Y, Giri U, Tumula PK, Nilsson MB, Gudikote J, Tran H, Cardnell RJ, Bearss DJ, Warner SL, Foulks JM, Kanner SB, Gandhi V, Krett N, Rosen ST, Kim ES, Herbst RS, Blumenschein GR, Lee JJ, Lippman SM, Ang KK, Mills GB, Hong WK, Weinstein JN, Wistuba II, Coombes KR, Minna JD, Heymach JV. An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance. Clinical Cancer Research 2013, 19: 279-290. PMID: 23091115, PMCID: PMC3567921, DOI: 10.1158/1078-0432.ccr-12-1558.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxl Receptor Tyrosine KinaseCarcinoma, Non-Small-Cell LungCell Line, TumorCluster AnalysisDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionErbB ReceptorsGene Expression ProfilingHumansLung NeoplasmsMiceNeoplasm MetastasisPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProteomeProteomicsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesRecurrenceReproducibility of ResultsConceptsEpithelial-mesenchymal transitionPotential therapeutic targetEGFR inhibitor resistanceTherapeutic targetEMT signatureInhibitor resistanceMesenchymal transition gene signatureMesenchymal cellsCell linesBiomarker-Integrated ApproachesPI3K/Akt pathway inhibitorNon-small cell lung carcinoma cell lineEGFR mutation statusReceptor tyrosine kinase AXLNSCLC cell linesPI3K/Akt inhibitorCell lung carcinoma cell lineGene expression profilesTyrosine kinase AXLLung carcinoma cell linePI3K inhibitorsDrug response analysisAkt pathway inhibitorCarcinoma cell linesErlotinib resistance
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 therapy
2006
Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor–independent urokinase-type plasminogen activator inhibition
Oh SH, Lee OH, Schroeder CP, Oh YW, Ke S, Cha HJ, Park RW, Onn A, Herbst RS, Li C, Lee HY. Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor–independent urokinase-type plasminogen activator inhibition. Molecular Cancer Therapeutics 2006, 5: 2685-2695. PMID: 17121915, DOI: 10.1158/1535-7163.mct-06-0142.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorFemaleFibroblastsHumansInsulin-Like Growth Factor Binding Protein 3Lung NeoplasmsMatrix Metalloproteinase 2Matrix Metalloproteinase InhibitorsMiceMice, NudeNeoplasm MetastasisNIH 3T3 CellsReceptor, IGF Type 1Recombinant ProteinsSignal TransductionUrokinase-Type Plasminogen ActivatorConceptsNon-small cell lung cancerInsulin-like growth factorIGF-independent mechanismsIGFBP-3Recombinant IGFBP-3Expression/activityLung cancerNSCLC cellsMajor IGF-binding proteinProtein 3H1299 cellsLung cancer cell metastasisGrowth factorInvasion of H1299Experimental animal model systemsCell lung cancerIGF-binding proteinsLung cancer metastasisA549 NSCLC cellsMatrix metalloproteinase-2Anti-invasive activityHuman lung fibroblastsCancer cell metastasisAnimal model systemsPlasminogen activator inhibition
2003
Development of an orthotopic model to study the biology and therapy of primary human lung cancer in nude mice.
Onn A, Isobe T, Itasaka S, Wu W, O'Reilly MS, Ki Hong W, Fidler IJ, Herbst RS. Development of an orthotopic model to study the biology and therapy of primary human lung cancer in nude mice. Clinical Cancer Research 2003, 9: 5532-9. PMID: 14654533.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Non-Small-Cell LungCarcinoma, Small CellCarcinoma, Squamous CellCell Line, TumorFibroblast Growth Factor 2HumansInterleukin-8Lung NeoplasmsLymphatic MetastasisMiceMice, NudeModels, BiologicalNeoplasm MetastasisNeovascularization, PathologicPaclitaxelVascular Endothelial Growth Factor AConceptsNon-small cell lung cancerHuman lung cancerCell lung cancerLung cancerOrthotopic modelNude miceHuman primary lung cancerPrimary human lung cancersSmall cell lung cancer cellsExtrathoracic lymph nodesCell lung cancer cellsPrimary lung cancerSquamous cell carcinomaLung cancer cell linesLung cancer biologyVascular endothelial growth factor/vascular permeability factorLimited therapeutic responseRelevant animal modelsNovel therapeutic strategiesBasic fibroblast growth factorCell lung cancer biologyHuman lung adenocarcinomaLung cancer cellsLung cancer tumorsVascular permeability factor
2002
The role of the epidermal growth factor receptor in the treatment of colorectal carcinoma
Waxman ES, Herbst RS. The role of the epidermal growth factor receptor in the treatment of colorectal carcinoma. Seminars In Oncology Nursing 2002, 18: 20-29. PMID: 12053861, DOI: 10.1053/sonu.2002.33072.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorColorectal carcinomaGrowth factor receptorClinical experienceAnti-EGFR monoclonal antibodiesTraditional cytotoxic approachesFactor receptorExtensive clinical testingTyrosine kinase inhibitorsEarly clinical experienceVariety of tumorsSignificant antitumor activityBiological agentsTreatment of cancerCytotoxic approachesEGFR resultsClinical testingNursing practiceCarcinomaMonoclonal antibodiesEGFR pathwayKinase inhibitorsAntitumor activityVariety of mechanismsReceptorsEpidermal growth factor receptors as a target for cancer treatment: The emerging role of IMC-C225 in the treatment of lung and head and neck cancers
Herbst RS, Langer CJ. Epidermal growth factor receptors as a target for cancer treatment: The emerging role of IMC-C225 in the treatment of lung and head and neck cancers. Seminars In Oncology 2002, 29: 27-36. PMID: 11894011, DOI: 10.1053/sonc.2002.31525.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCetuximabCombined Modality TherapyErbB ReceptorsGene Expression Regulation, NeoplasticHalf-LifeHead and Neck NeoplasmsHumansNeoplasm MetastasisNeoplasm Recurrence, LocalRadiation-Sensitizing AgentsRandomized Controlled Trials as TopicSalvage TherapyConceptsSquamous cell carcinomaEpidermal growth factor receptorIMC-C225Phase II trialGrowth factor receptorCell carcinomaII trialFactor receptorRadiation therapyNon-small cell lung cancer xenograftsNon-small cell lung cancerGemcitabine/carboplatin combinationSeparate phase II trialsAdvanced squamous cell carcinomaCell lung cancer xenograftsOngoing phase II trialEastern Cooperative Oncology GroupPhase III registration trialPhase I pharmacokinetic studyCultured human squamous cell carcinomasHuman squamous cell carcinomaPaclitaxel/carboplatinSecond-line settingStandard salvage regimensTreatment-naive patients
2001
Lung cancer in patients under age 40
Skarin A, Herbst R, Leong T, Bailey A, Sugarbaker D. Lung cancer in patients under age 40. Lung Cancer 2001, 32: 255-264. PMID: 11390007, DOI: 10.1016/s0169-5002(00)00233-6.Peer-Reviewed Original ResearchConceptsStage IV diseaseSmall cell carcinomaSquamous cell carcinomaCell carcinomaPerformance statusStage IIIBStage IIIAOlder patientsLung cancerYear survivalAge 40Stage I/IIDana-Farber Cancer InstituteGreater body weight lossWeight lossECOG performance statusPercent of patientsPoor performance statusDuration of symptomsSite of metastasisOverall patient survivalStage of diseaseBody weight lossAbsence of symptomsPercentage of women
2000
Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage I non-small cell lung carcinoma.
Herbst RS, Yano S, Kuniyasu H, Khuri FR, Bucana CD, Guo F, Liu D, Kemp B, Lee JJ, Hong WK, Fidler IJ. Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage I non-small cell lung carcinoma. Clinical Cancer Research 2000, 6: 790-7. PMID: 10741698.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCadherinsCarcinoma, Non-Small-Cell LungDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansIn Situ HybridizationLung NeoplasmsMaleMatrix Metalloproteinase 2Matrix Metalloproteinase 9Middle AgedMultivariate AnalysisNeoplasm MetastasisNeoplasm Recurrence, LocalNeoplasm StagingPredictive Value of TestsSurvival AnalysisConceptsE-cadherin ratioLung cancerType IV collagenaseLung carcinomaDisease outcomeStage I non-small cell lung carcinomaPrimary non-small cell lung cancerNon-small cell lung cancerE-cadherinKaplan-Meier survival analysisNon-small cell lung carcinomaD. Anderson Cancer CenterResectable lung cancerDisease-free survivalSignificant prognostic factorsLonger overall survivalCell lung cancerDisease recurrence rateRoutine histopathological examinationCox univariate analysisAnderson Cancer CenterCell lung carcinomaVascular endothelial growth factor/vascular permeability factorHuman lung cancerBasic fibroblast growth factor