2022
BFAST but be smart: bTMB remains an exploratory biomarker in NSCLC
Kim SY, Herbst RS. BFAST but be smart: bTMB remains an exploratory biomarker in NSCLC. Nature Reviews Clinical Oncology 2022, 20: 3-4. PMID: 36271141, DOI: 10.1038/s41571-022-00698-y.Peer-Reviewed Original ResearchConceptsCell lung cancerTumor mutational burdenLung cancerMutational burdenBlood-based tumor mutational burdenAdvanced-stage solid tumorsFirst phase III trialHigh tumor mutational burdenImmune checkpoint inhibitorsPhase III trialsIII trialsPredictive biomarkersExploratory biomarkersCompanion biomarkersSolid tumorsBiomarkersCancerBurdenPembrolizumabNSCLCPatientsTumorsTrialsAdaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities
Kim TK, Vandsemb EN, Herbst RS, Chen L. Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities. Nature Reviews Drug Discovery 2022, 21: 529-540. PMID: 35701637, DOI: 10.1038/s41573-022-00493-5.Peer-Reviewed Original ResearchConceptsAdaptive immune resistanceImmune resistanceCell death 1 ligand 1Tumor siteDeath 1 ligand 1Anti-PD therapyBlockade of PDL1Advanced-stage cancerFraction of patientsStrong mechanistic rationaleFuture drug developmentCurrent cancer therapiesImmune attackClinical trialsSolid tumorsTherapeutic opportunitiesTumorsCancer therapySelective inductionAntitumour drugsLigand 1Drug developmentTherapyAdditive effectMechanistic rationale
2020
Comprehensive T cell repertoire characterization of non-small cell lung cancer
Reuben A, Zhang J, Chiou SH, Gittelman RM, Li J, Lee WC, Fujimoto J, Behrens C, Liu X, Wang F, Quek K, Wang C, Kheradmand F, Chen R, Chow CW, Lin H, Bernatchez C, Jalali A, Hu X, Wu CJ, Eterovic AK, Parra ER, Yusko E, Emerson R, Benzeno S, Vignali M, Wu X, Ye Y, Little LD, Gumbs C, Mao X, Song X, Tippen S, Thornton RL, Cascone T, Snyder A, Wargo JA, Herbst R, Swisher S, Kadara H, Moran C, Kalhor N, Zhang J, Scheet P, Vaporciyan AA, Sepesi B, Gibbons DL, Robins H, Hwu P, Heymach JV, Sharma P, Allison JP, Baladandayuthapani V, Lee JJ, Davis MM, Wistuba II, Futreal PA, Zhang J. Comprehensive T cell repertoire characterization of non-small cell lung cancer. Nature Communications 2020, 11: 603. PMID: 32001676, PMCID: PMC6992630, DOI: 10.1038/s41467-019-14273-0.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerT cellsLung cancerAdoptive T-cell therapyEarly-stage NSCLC patientsT cell repertoire analysisT cell responsesLungs of patientsT-cell therapyNSCLC patientsInferior survivalClinicopathologic featuresImmune landscapeViral infectionSolid tumorsTherapeutic efficacyCell responsesCell therapyPatientsRepertoire analysisLungTumorsImmunotherapyConsiderable proportion
2018
Activity of ramucirumab (R) with pembrolizumab (P) by PD-L1 expression in advanced solid tumors: Phase 1a/b study in later lines of therapy.
Herbst R, Chau I, Petrylak D, Arkenau H, Bendell J, Santana-Davila R, Calvo E, Penel N, Martin-Liberal J, Soriano A, Cassier P, Krebs M, Isambert N, Widau R, Mi G, Jin J, Ferry D, Fuchs C, Paz-Ares L. Activity of ramucirumab (R) with pembrolizumab (P) by PD-L1 expression in advanced solid tumors: Phase 1a/b study in later lines of therapy. Journal Of Clinical Oncology 2018, 36: 3059-3059. DOI: 10.1200/jco.2018.36.15_suppl.3059.Peer-Reviewed Original Research
2015
Targeted Therapy in Solid Tumors: Lung Cancer
Waqar S, Morgensztern D, Herbst R. Targeted Therapy in Solid Tumors: Lung Cancer. 2015, 224-230. DOI: 10.1002/9781118468678.ch23.Peer-Reviewed Original ResearchNon-small cell lung cancerLung cancerManagement of NSCLCMetastatic non-small cell lung cancerChoice of regimensUnprecedented response ratesProgression-free survivalEarly-stage diseaseIncurable metastatic diseaseCell lung cancerImproved cure ratesToxic treatment optionsMetastatic diseaseStage diseaseCure rateTreatment optionsTargeted therapyToxicity profileSecondary resistanceResponse rateSolid tumorsPatientsTumor progressionTherapyTumors
2014
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014, 515: 563-567. PMID: 25428504, PMCID: PMC4836193, DOI: 10.1038/nature14011.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkersChemokine CX3CL1Clinical ProtocolsCTLA-4 AntigenDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasmsTreatment OutcomeYoung AdultNew Strategies in Personalized Medicine for Solid Tumors: Molecular Markers and Clinical Trial Designs
Jürgensmeier JM, Eder JP, Herbst RS. New Strategies in Personalized Medicine for Solid Tumors: Molecular Markers and Clinical Trial Designs. Clinical Cancer Research 2014, 20: 4425-4435. PMID: 25183480, PMCID: PMC5369358, DOI: 10.1158/1078-0432.ccr-13-0753.Peer-Reviewed Original ResearchConceptsClinical trialsTumor biologyFuture patient selectionTherapy of patientsOngoing clinical evaluationBroad molecular profilingPromising tumor targetPersonalized medicinePatient selectionPatient populationTreatment recommendationsClinical evaluationTumor boardClinical studiesImmune parametersNovel agentsTumor targetsTreatment approachesSolid tumorsClinical researchPatientsMolecular profilingSpecific markersTumorsTrials
2013
A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors.
Herbst R, Gordon M, Fine G, Sosman J, Soria J, Hamid O, Powderly J, Burris H, Mokatrin A, Kowanetz M, Leabman M, Anderson M, Chen D, Hodi F. A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors. Journal Of Clinical Oncology 2013, 31: 3000-3000. DOI: 10.1200/jco.2013.31.15_suppl.3000.Peer-Reviewed Original ResearchPD-L1RECIST responseSolid tumorsTumor-specific T cell immunityPD-L1 tumor statusDose-escalation cohortsTumor PD-L1PD-L1 antibodiesCancer immune evasionMetastatic solid tumorsT cell immunityPD ratePD-L1 bindingHuman monoclonal antibodyVariety of tumorsMultiple tumor typesProlonged SDsRECIST v1.1Expansion cohortDurable responsesMedian durationRadiographic progressionPD-1Negative tumorsTumor shrinkagePhase 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 EGFR
2012
Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours
Martin LP, Kozloff MF, Herbst RS, Samuel TA, Kim S, Rosbrook B, Tortorici M, Chen Y, Tarazi J, Olszanski AJ, Rado T, Starr A, Cohen RB. Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours. British Journal Of Cancer 2012, 107: 1268-1276. PMID: 22996612, PMCID: PMC3494424, DOI: 10.1038/bjc.2012.407.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsCommon treatment-related adverse eventsSolid tumorsTreatment-related adverse eventsAntitumour activitySelective second-generation inhibitorPhase ICo-administered agentsVascular endothelial growth factor receptorHand-foot syndromeEndothelial growth factor receptorHuman xenograft tumor modelsEfficacy of chemotherapyXenograft tumor modelMultiple tumor typesAxitinib pharmacokineticsCapecitabine pharmacokineticsGrowth factor receptorStable diseaseStarting doseAdverse eventsPartial responseComplete responseTreatment regimenDocetaxel exposurePhase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours
Kozloff MF, Martin LP, Krzakowski M, Samuel TA, Rado TA, Arriola E, De Castro Carpeño J, Herbst RS, Tarazi J, Kim S, Rosbrook B, Tortorici M, Olszanski AJ, Cohen RB. Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours. British Journal Of Cancer 2012, 107: 1277-1285. PMID: 22990652, PMCID: PMC3494447, DOI: 10.1038/bjc.2012.406.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPaclitaxel/carboplatinAdvanced non-small cell lung cancerPharmacokinetics of axitinibGemcitabine/cisplatinCell lung cancerAxitinib 5Platinum doubletsLung cancerSolid tumorsSquamous cell non-small cell lung cancerTreatment-related adverse eventsSelective second-generation inhibitorVascular endothelial growth factor receptorObjective response rateDose-limiting toxicityPhase I trialEndothelial growth factor receptorDose-finding trialDrug-drug interactionsPhase I dose-finding trialsCisplatin regimensFebrile neutropeniaGrowth factor receptorExpansion cohortA Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors
Hong DS, Bowles DW, Falchook GS, Messersmith WA, George GC, O'Bryant CL, Vo AC, Klucher K, Herbst RS, Eckhardt SG, Peterson S, Hausman DF, Kurzrock R, Jimeno A. A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors. Clinical Cancer Research 2012, 18: 4173-4182. PMID: 22693357, DOI: 10.1158/1078-0432.ccr-12-0714.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAged, 80 and overArea Under CurveDiarrheaDisease ProgressionDose-Response Relationship, DrugDrug Administration ScheduleEnzyme InhibitorsFatigueFemaleGonanesHumansMaleMetabolic Clearance RateMiddle AgedMutationNauseaNeoplasmsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsTreatment OutcomeVomitingConceptsDose-limiting toxicityArm 1PX-866Stable diseaseArm 2Frequent study drug-related adverse eventsSolid tumorsStudy drug-related adverse eventsDrug-related adverse eventsMulticenter phase I trialGrade III diarrheaAdvanced solid tumorsDose-escalation studyResponse Evaluation CriteriaContinuous dosing scheduleElevated aspartate aminotransferasePhase I trialEvaluable patientsIrreversible small-molecule inhibitorAdverse eventsDosing schedulesI trialAdditional patientsGastrointestinal disordersIncurable cancer
2011
A Phase I study to assess the safety, tolerability, and pharmacokinetics of AZD4877, an intravenous Eg5 inhibitor in patients with advanced solid tumors
Infante JR, Kurzrock R, Spratlin J, Burris HA, Eckhardt SG, Li J, Wu K, Skolnik JM, Hylander-Gans L, Osmukhina A, Huszar D, Herbst RS. A Phase I study to assess the safety, tolerability, and pharmacokinetics of AZD4877, an intravenous Eg5 inhibitor in patients with advanced solid tumors. Cancer Chemotherapy And Pharmacology 2011, 69: 165-172. PMID: 21638123, DOI: 10.1007/s00280-011-1667-z.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPrimary dose-limiting toxicityPhase IAcceptable safety profileAdvanced solid malignanciesAdvanced solid tumorsRelated adverse eventsSeverity of neutropeniaConclusionThe MTDAdverse eventsIntravenous infusionSafety profileSolid malignanciesAZD4877Intermediate doseDose reductionPart BPharmacokinetic profileDay 1Solid tumorsPart ANeutropeniaTolerabilityPatientsMTD
2010
A First-in-Human Study of Conatumumab in Adult Patients with Advanced Solid Tumors
Herbst RS, Kurzrock R, Hong DS, Valdivieso M, Hsu CP, Goyal L, Juan G, Hwang YC, Wong S, Hill JS, Friberg G, LoRusso PM. A First-in-Human Study of Conatumumab in Adult Patients with Advanced Solid Tumors. Clinical Cancer Research 2010, 16: 5883-5891. PMID: 20947515, DOI: 10.1158/1078-0432.ccr-10-0631.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced solid tumorsPartial responseColorectal cancerStable diseaseSolid tumorsPositron emission tomographic scansHuman death receptor 5Dose-expansion phaseGrade 3 eventsDose-escalation phaseCell lung cancerStandardized uptake valueHuman monoclonal agonist antibodyMonoclonal agonist antibodyDeath receptor 5Week 96Adult patientsAdverse eventsIntravenous dosesMore dosesTumor sizeLung cancerTumor levelsTumor responseFirst-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients (pts) with advanced solid tumors.
Burris H, Rodon J, Sharma S, Herbst R, Tabernero J, Infante J, Silva A, Demanse D, Hackl W, Baselga J. First-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2010, 28: 3005-3005. DOI: 10.1200/jco.2010.28.15_suppl.3005.Peer-Reviewed Original Research
2009
Targeted drug delivery strategies to treat lung metastasis
Bar J, Herbst RS, Onn A. Targeted drug delivery strategies to treat lung metastasis. Expert Opinion On Drug Delivery 2009, 6: 1003-1016. PMID: 19663628, DOI: 10.1517/17425240903167926.Peer-Reviewed Original ResearchConceptsLung metastasesStandard clinical useMetastatic diseaseClinical trialsClinical useMost cancer patientsEarly clinical studiesCancer-specific antibodiesDrug delivery strategiesMain tumorTargeted drug delivery strategiesCancer patientsClinical studiesIntravascular devicesSolid tumorsMetastasisPreclinical developmentVascular fieldTreatmentTherapyTumorsAnticancer toolDiseaseDelivery strategiesTrialsSafety, 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 profileTumor Blood Flow Measured by Perfusion Computed Tomography and 15O-Labeled Water Positron Emission Tomography
Ng CS, Kodama Y, Mullani NA, Barron BJ, Wei W, Herbst RS, Abbruzzese JL, Charnsangavej C. Tumor Blood Flow Measured by Perfusion Computed Tomography and 15O-Labeled Water Positron Emission Tomography. Journal Of Computer Assisted Tomography 2009, 33: 460-465. PMID: 19478644, DOI: 10.1097/rct.0b013e318182d2e0.Peer-Reviewed Original ResearchConceptsWater positron emission tomographyPositron emission tomographyBlood flowEmission tomographyMean blood flow valuesBlood flow estimatesPerfusion Computed TomographyTumor blood flowPairs of examinationsBlood flow valuesMixed regression analysesUse of PCTBlood flow measurementsClinical gold standardIndex tumorClinical studiesComputed tomographySolid tumorsTumorsGold standardBland-AltmanTomographySignificant differencesRegression analysisT-test
2008
Clinical, pharmacokinetic (PK), pharmacodynamic findings in a phase I trial of weekly (wkly) intravenous AZD4877 in patients with refractory solid tumors
Infante J, Spratlin J, Kurzrock R, Eckhardt S, Burris H, Puchalski T, Li J, Wu K, Ochs J, Herbst R. Clinical, pharmacokinetic (PK), pharmacodynamic findings in a phase I trial of weekly (wkly) intravenous AZD4877 in patients with refractory solid tumors. Journal Of Clinical Oncology 2008, 26: 2501-2501. DOI: 10.1200/jco.2008.26.15_suppl.2501.Peer-Reviewed Original ResearchPhase I multicenter trial of BMS-690514: Safety, pharmacokinetic profile, biological effects, and early clinical evaluation in patients with advanced solid tumors and non-small cell lung cancer
Bahleda R, Felip E, Herbst R, Hanna N, Laurie S, Shepherd F, Armand J, Sweeney C, Calvo-Aller E, Soria J. Phase I multicenter trial of BMS-690514: Safety, pharmacokinetic profile, biological effects, and early clinical evaluation in patients with advanced solid tumors and non-small cell lung cancer. Journal Of Clinical Oncology 2008, 26: 2564-2564. DOI: 10.1200/jco.2008.26.15_suppl.2564.Peer-Reviewed Original Research