2023
SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei H, de Marinis F, Dumoulin D, Reynolds C, Theelen W, Percent I, Calderon V, Johnson M, Madroszyk-Flandin A, Garon E, He K, Planchard D, Reck M, Popat S, Herbst R, Leal T, Shazer R, Yan X, Harrigan R, Peters S, Investigators S, Abdel-Karim I, Abdelsalam M, Addeo A, Aguado C, Alexander P, Alt J, Azzi G, Balaraman R, Biesma B, Blackhall F, Bohnet S, Boleti E, Borghaei H, Bradbury P, Brighenti M, Campbell N, Campbell T, Canon J, Cappuzzo F, Costa E, Cavanna L, Cetnar J, Chella A, Chouaid C, Christoph D, Castán J, Dakhil S, de Castro Carpeño F, de Marinis F, Delmonte A, Demedts I, Demey W, Dits J, del Pilar Diz Taín M, Gómez M, Dorius T, Dumoulin D, Duruisseaux M, Eaton K, González E, Evans D, Faehling M, Farrell N, Feinstein T, Font E, Campelo M, Garon E, López M, Germonpré P, Gersten T, Cao M, Gopaluni S, Greillier L, Grossi F, Guisier F, Gurubhagavatula S, Calderón V, Hakimian D, Hall R, Hao D, Harris R, Hashemi S, He K, Hendriks L, Huang C, Ibrahim E, Jain S, Johnson M, Jones B, Jones M, Vidal Ó, Juergens R, Kaderbhai C, Kastelijn E, Keresztes R, Kio E, Kokowski K, Konduri K, Kulkarni S, Kuon J, Kurkjian C, Labbé C, Lerner R, Lim F, Madroszyk-Flandin A, Marathe O, Martincic D, McClay E, McIntyre K, Mekhail T, Misino A, Molinier O, Morabito A, Morócz É, Müller V, Nagy T, Nguyen A, Nidhiry E, Okazaki I, Ortega-Granados A, Ostoros G, Oubre D, Owen S, Pachipala K, Park D, Patel P, Percent I, Pérol M, Peters S, Piet B, Planchard D, Polychronis A, Aix S, Pons-Tostivint E, Popat S, Pulla M, Quantin X, Quéré G, Rafique N, Ramaekers R, Reck M, Reiman A, Reinmuth N, Reynolds C, Rodríguez-Abreu D, Romano G, Roque T, Salzberg M, Sanborn R, Sandiego S, Schaefer E, Schreeder M, Seetharamu N, Seneviratne L, Shah P, Shunyakov L, Slater D, Parra H, Stigt J, Stilwill J, Su J, Surmont V, Swink A, Szalai Z, Talbot T, Garcia A, Theelen W, Thompson J, Tiseo M, Uprety D, Uyeki J, van der Leest K, Van Ho A, van Putten J, Estévez S, Veatch A, Vergnenègre A, Ward P, Weise A, Weiss M, Whitehurst M, Zai S, Zalcman G, Zuniga R. SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. Annals Of Oncology 2023, 35: 66-76. PMID: 37866811, DOI: 10.1016/j.annonc.2023.10.004.Peer-Reviewed Original ResearchClinical benefit rateObjective response rateProgression-free survivalCell lung cancerOverall survivalNonsquamous NSCLCPrimary endpointLung cancerMedian progression-free survivalTreatment-related adverse eventsReceptor tyrosine kinase inhibitorsAdvanced nonsquamous NSCLCCheckpoint inhibitor therapyMedian overall survivalPlatinum-based chemotherapyDuration of responseImmunosuppressive tumor microenvironmentTyrosine kinase inhibitorsImmunostimulatory stateMedian DoRSecondary endpointsMost patientsAdverse eventsInhibitor therapySafety profile
2022
Spatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small-cell lung cancer
Moutafi MK, Molero M, Morilla S, Baena J, Vathiotis IA, Gavrielatou N, Castro-Labrador L, de Garibay GR, Adradas V, Orive D, Valencia K, Calvo A, Montuenga LM, Aix S, Schalper KA, Herbst RS, Paz-Ares L, Rimm DL, Zugazagoitia J. Spatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small-cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e004757. PMID: 36002182, PMCID: PMC9413286, DOI: 10.1136/jitc-2022-004757.Peer-Reviewed Original ResearchConceptsProgression-free survivalPD-1 axis blockadePD-1 axis inhibitorsTumor proportion scoreCell lung cancerAxis blockadeQuantitative immunofluorescenceAxis inhibitionLung cancerCD44 levelsCD44 expressionTumor compartmentsLonger progression-free survivalAbsence of immunotherapyYale Cancer CenterWhole tissue sectionsQIF scoresExternal independent validationMost patientsOverall survivalTim-3Immune compartmentImmunotherapy strategiesPD-L1Untreated cohort
2018
Chapter 6 Management of Advanced Non–Small Cell Lung Cancer Noncurative Intent Treatment
Xia B, Herbst R. Chapter 6 Management of Advanced Non–Small Cell Lung Cancer Noncurative Intent Treatment. 2018, 99-115. DOI: 10.1016/b978-0-323-48565-4.00006-0.Peer-Reviewed Original ResearchNon-small cell lung cancerPD-L1 expressionPlatinum-based chemotherapyTreatment optionsLung cancerFirst-line systemic treatment optionMolecular alterationsSecond-line settingSystemic treatment optionsTime of diagnosisMain treatment optionCell lung cancerCancer-related mortalityBiomarkers of responseEfficacy of treatmentAbstract Lung cancerAdenocarcinoma histologyIntent treatmentMetastatic diseaseMost patientsClinical outcomesNoninvasive testingClinical trialsNovel therapiesTreatment strategies
2017
Immune Checkpoint Inhibition in Lung Cancer
Morgensztern D, Herbst R. Immune Checkpoint Inhibition in Lung Cancer. 2017, 333-344. DOI: 10.1007/978-3-319-62431-0_20.Peer-Reviewed Original ResearchNon-small cell carcinomaSmall cell lung cancerLarge cell carcinomaSquamous cell carcinomaVascular endothelium growth factorLung cancerCell carcinomaEpidermal growth factor receptorMost patientsMetastatic non-small cell carcinomaPlatinum-based chemotherapy doubletsSmall molecule tyrosine kinase inhibitorsMolecule tyrosine kinase inhibitorsAbsence of contraindicationsImmune checkpoint inhibitionProlonged clinical benefitCell lung cancerStandard of careAmerican Cancer SocietyTyrosine kinase inhibitorsChemotherapy doubletsGrowth factor receptorNSCLC presentPalliative intentCheckpoint inhibitionMeasurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers.
Datar I, Mani N, Henick B, Wurtz A, Kaftan E, Herbst R, Rimm D, Gettinger S, Politi K, Schalper K. Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers. Journal Of Clinical Oncology 2017, 35: e14611-e14611. DOI: 10.1200/jco.2017.35.15_suppl.e14611.Peer-Reviewed Original ResearchNon-small cell lung carcinomaTim-3PD-1LAG-3T cellsInhibitory receptorsAdvanced non-small cell lung carcinomaPD-1 axis blockadeHigh TIM-3Immune suppressive pathwaysImmune inhibitory receptorsCell lung carcinomaMembranous staining patternPre-treatment samplesWhole tissue sectionsWhole tumor areaClinical responseMost patientsAxis blockadeLow levelsLung carcinomaT lymphocytesMultiplex immunofluorescenceHigh levelsSuppressive pathways
2014
119IN Novel Molecular Studies to Inform the Conduct of Oncology Clinical Trials: from Battle to Master Protocols
Herbst R. 119IN Novel Molecular Studies to Inform the Conduct of Oncology Clinical Trials: from Battle to Master Protocols. Annals Of Oncology 2014, 25: iv41. DOI: 10.1093/annonc/mdu317.1.Peer-Reviewed Original ResearchLung cancer patientsCancer patientsSquamous cell lung cancer patientsMaster protocolsMulticenter phase 2 trialCell lung cancer patientsNovel molecular studiesPhase 2 trialScreen failure rateOncology clinical trialsCause of deathEffective treatment regimensIdentification of therapiesClinical trial researchIndividual patient's cancerSystemic chemotherapyClinical characteristicsMetastatic diseaseMost patientsPerformance statusTreatment regimensMultiple therapiesClinical trialsAdaptive randomization designPatient's cancer
2010
A Phase I Safety and Pharmacokinetic Study of the Death Receptor 5 Agonistic Antibody PRO95780 in Patients with Advanced Malignancies
Camidge DR, Herbst RS, Gordon MS, Eckhardt SG, Kurzrock R, Durbin B, Ing J, Tohnya TM, Sager J, Ashkenazi A, Bray G, Mendelson D. A Phase I Safety and Pharmacokinetic Study of the Death Receptor 5 Agonistic Antibody PRO95780 in Patients with Advanced Malignancies. Clinical Cancer Research 2010, 16: 1256-1263. PMID: 20145186, DOI: 10.1158/1078-0432.ccr-09-1267.Peer-Reviewed Original ResearchConceptsAdvanced malignanciesGrade 3 transaminase elevationHuman IgG1 monoclonal antibodyPhase I safetyDose-escalation designDose-dependent increaseDeath receptor 5Different tumor typesIgG1 monoclonal antibodyCohort expansionTransaminase elevationI safetyMost patientsObjective responseTrough concentrationsAdverse eventsEscalation designMultiple dosesMinor responseEfficacious concentrationsOvarian cancerEvidence of activityPharmacokinetic analysisReceptor 5Human studies
2009
Beyond Doublet Chemotherapy for Advanced Non–Small-Cell Lung Cancer: Combination of Targeted Agents with First-Line Chemotherapy
Herbst RS, Lynch TJ, Sandler AB. Beyond Doublet Chemotherapy for Advanced Non–Small-Cell Lung Cancer: Combination of Targeted Agents with First-Line Chemotherapy. Clinical Lung Cancer 2009, 10: 20-27. PMID: 19289368, DOI: 10.3816/clc.2009.n.003.Peer-Reviewed Original ResearchConceptsBest supportive careOverall survivalMetastatic NSCLCLung cancerAdvanced non-small cell lung cancerNon-small cell lung cancerPhase III clinical trialsPlatinum-based doubletsAddition of bevacizumabFirst-line chemotherapyPlatinum-based regimensProgression-free survivalFirst-line treatmentCell lung cancerOverall patient survivalTyrosine kinase inhibitorsInhibition of componentsMatrix metalloproteinase inhibitorsDoublet chemotherapySystemic chemotherapyMedian survivalSupportive careMost patientsTargeted agentsChemotherapeutic regimens
2005
Angiogenesis and lung cancer: prognostic and therapeutic implications.
Herbst RS, Onn A, Sandler A. Angiogenesis and lung cancer: prognostic and therapeutic implications. Journal Of Clinical Oncology 2005, 23: 3243-56. PMID: 15886312, DOI: 10.1200/jco.2005.18.853.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorAntiangiogenic agentsLung cancerSurrogate markerProangiogenic vascular endothelial growth factorMajority of patientsReliable surrogate markerTumor vascular developmentDownstream receptor signalingKey therapeutic strategyEndothelial growth factorVEGF receptor bindingMetastatic diseaseMost patientsCancer deathConventional chemotherapyCommon causeTherapeutic strategiesTherapeutic implicationsTumor typesTumor vasculatureTarget inhibitionAnticancer effectsCytostatic effectReceptor signalingClinically Meaningful Improvement in Symptoms and Quality of Life for Patients With Non-Small-Cell Lung Cancer Receiving Gefitinib in a Randomized Controlled Trial
Cella D, Herbst RS, Lynch TJ, Prager D, Belani CP, Schiller JH, Heyes A, Ochs JS, Wolf MK, Kay AC, Kris MG, Natale RB. Clinically Meaningful Improvement in Symptoms and Quality of Life for Patients With Non-Small-Cell Lung Cancer Receiving Gefitinib in a Randomized Controlled Trial. Journal Of Clinical Oncology 2005, 23: 2946-2954. PMID: 15699477, DOI: 10.1200/jco.2005.05.153.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overAntineoplastic AgentsCarcinoma, Non-Small-Cell LungDose-Response Relationship, DrugDouble-Blind MethodEndpoint DeterminationFemaleGefitinibHealth StatusHumansLung NeoplasmsMaleMiddle AgedQuality of LifeQuinazolinesSensitivity and SpecificitySurvival AnalysisConceptsLung Cancer SubscaleSymptom improvementTumor responseQuality of lifeCancer Therapy-Lung (FACT-L) questionnairePivotal phase II trialMedian overall survival timeCoprimary end pointsPrior chemotherapy regimensProtocol-specified analysisSymptom improvement ratePhase II trialBetter overall survivalCell lung cancerOverall survival timeGefitinib 250Radiographic regressionChemotherapy regimensStable diseaseII trialMost patientsOverall survivalRadiographic responseSymptomatic patientsNSCLC patients
2003
Dermatologic Side Effects Associated with Gefitinib Therapy: Clinical Experience and Management
Herbst RS, LoRusso PM, Purdom M, Ward D. Dermatologic Side Effects Associated with Gefitinib Therapy: Clinical Experience and Management. Clinical Lung Cancer 2003, 4: 366-369. PMID: 14599302, DOI: 10.3816/clc.2003.n.016.Peer-Reviewed Original ResearchDermatologic effectsGefitinib treatmentClinical trialsDry skinSide effectsFrequent drug-related adverse effectsDrug-related allergic reactionsRecent phase II trialDrug-related adverse effectsAdverse effectsDermatologic adverse effectsPhase II trialDermatologic side effectsCell lung cancerNumerous clinical trialsSimilar side effectsVariety of treatmentsMechanism of actionAcneiform rashTopical clindamycinAdvanced NSCLCEpidermal growth factor receptor tyrosine kinaseII trialMost patientsGefitinib therapyHead and neck cancer
Kies M, Herbst R. Head and neck cancer. 2003, 207-216. DOI: 10.1017/cbo9780511527081.025.Peer-Reviewed Original ResearchSquamous cell cancerNeck malignanciesCell cancerNeck cancerTobacco useNeck squamous cell cancerIndependent risk factorEpstein-Barr virusFloor of mouthConsumption of fruitsDose-response relationshipSynergistic carcinogenic effectUncommon headAdvanced diseaseMost patientsMedian ageAnnual incidenceViral exposureCommon cancerRisk factorsTreatment outcomesIntroduction HeadBuccal mucosaNasopharyngeal carcinomaOral cavityIntegration of Targeted Therapies in Gemcitabine Chemotherapy Regimens
Blumenschein GR, Herbst RS. Integration of Targeted Therapies in Gemcitabine Chemotherapy Regimens. Clinical Lung Cancer 2003, 4: 217-223. PMID: 14624709, DOI: 10.3816/clc.2003.n.001.Peer-Reviewed Original ResearchLung cancerTargeted therapyCell lung cancerReceptor-targeted therapyLung cancer casesHigh mortality rateSpecific biologic pathwaysAdvanced NSCLCChemotherapy regimensCell cycle inhibitionMost patientsCommon malignancyPoor prognosisCancer casesTherapeutic improvementRadiation therapyEncouraging activityNew agentsMortality rateAngiogenesis inhibitionSingle agentClinical testingSurvival rateTherapyTargeted therapeuticsAngiogenesis, Metastasis, and Lung Cancer
Onn A, Herbst RS. Angiogenesis, Metastasis, and Lung Cancer. Methods In Molecular Medicine 2003, 74: 329-348. PMID: 12415706, DOI: 10.1385/1-59259-323-2:329.Peer-Reviewed Original ResearchConceptsNew blood vesselsBlood vesselsBlood supplyTumor angiogenesisPre-existing tumorsAdequate blood supplyNegative regulatory moleculeAnti-angiogenesis drugsInduction of angiogenesisMost patientsInitial treatmentConventional therapyDetectable metastasesLung cancerMost deathsCancer resultsMetastasisTumorsAngiogenesisStriking increaseCancer biologyCancerNormal cellsTerm angiogenesisHost cells