2022
Circulating Tumor DNA Kinetics Predict Progression-Free and Overall Survival in EGFR TKI–Treated Patients with EGFR-Mutant NSCLC (SWOG S1403)
Mack PC, Miao J, Redman MW, Moon J, Goldberg SB, Herbst RS, Melnick MA, Walther Z, Hirsch FR, Politi K, Kelly K, Gandara DR. Circulating Tumor DNA Kinetics Predict Progression-Free and Overall Survival in EGFR TKI–Treated Patients with EGFR-Mutant NSCLC (SWOG S1403). Clinical Cancer Research 2022, 28: 3752-3760. PMID: 35713632, PMCID: PMC9444942, DOI: 10.1158/1078-0432.ccr-22-0741.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalEGFR mutationsNon-small cell lung cancerCycle 3 day 1Median progression-free survivalMedian overall survivalRisk of progressionCell lung cancerPresence of brainEGFR-mutant NSCLCBaseline ctDNAM1b stageProgression-FreeRECIST responseSerial plasmaLiver metastasesDecreased riskEGFR-TKILung cancerComplete clearanceLong-term benefitsClinical trialsTreatment outcomesPlasma clearance
2020
Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of EGFR-Mutant Non-Small-Cell Lung Cancer: Final Results From SWOG S1403.
Goldberg SB, Redman MW, Lilenbaum R, Politi K, Stinchcombe TE, Horn L, Chen EH, Mashru SH, Gettinger SN, Melnick MA, Herbst RS, Baumgart MA, Miao J, Moon J, Kelly K, Gandara DR. Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of EGFR-Mutant Non-Small-Cell Lung Cancer: Final Results From SWOG S1403. Journal Of Clinical Oncology 2020, 38: 4076-4085. PMID: 33021871, PMCID: PMC7768342, DOI: 10.1200/jco.20.01149.Peer-Reviewed Original ResearchConceptsProgression-free survivalLung cancerMutant NSCLCEGFR monoclonal antibody cetuximabSmall cell lung cancerAddition of cetuximabPrimary end pointTyrosine kinase inhibitor afatinibCell lung cancerEGFR-Mutant NonCombination of afatinibMonoclonal antibody cetuximabAdvanced diseaseAdverse eventsOverall survivalMulticenter trialLine treatmentEGFR-TKIAntibody cetuximabDose reductionInhibitor afatinibInterim analysisCetuximabInsufficient evidencePatientsOsimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA.
Herbst R, Tsuboi M, John T, Grohé C, Majem M, Goldman J, Kim S, Marmol D, Rukazenkov Y, Wu Y. Osimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. Journal Of Clinical Oncology 2020, 38: lba5-lba5. DOI: 10.1200/jco.2020.38.18_suppl.lba5.Peer-Reviewed Original ResearchDisease-free survivalComplete tumor resectionDFS hazard ratioAdjuvant chemotherapyData cutoffHazard ratioOverall survivalTumor resectionAdjuvant osimertinibDFS ratesEGFRm NSCLCEGFR-TKISafety profileEGFR mutation-positive NSCLCEffective new treatment strategyResected stage IISafety of osimertinibEarly-stage diseaseMutation-positive NSCLCNew treatment strategiesUnplanned interim analysisEligible ptsIIIA NSCLCNSCLC presentPS 0/1
2017
Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers
Nilsson MB, Sun H, Diao L, Tong P, Liu D, Li L, Fan Y, Poteete A, Lim SO, Howells K, Haddad V, Gomez D, Tran H, Pena GA, Sequist LV, Yang JC, Wang J, Kim ES, Herbst R, Lee JJ, Hong WK, Wistuba I, Hung MC, Sood AK, Heymach JV. Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers. Science Translational Medicine 2017, 9 PMID: 29118262, PMCID: PMC5870120, DOI: 10.1126/scitranslmed.aao4307.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AntagonistsAfatinibAMP-Activated Protein Kinase KinasesCarcinoma, Non-Small-Cell LungCell Line, TumorCyclic AMP Response Element-Binding ProteinDrug Resistance, NeoplasmEpinephrineErbB ReceptorsHumansInterleukin-6Lung NeoplasmsMutationNorepinephrineProtein Kinase CProtein Kinase InhibitorsProtein Serine-Threonine KinasesQuinazolinesReceptors, Adrenergic, betaSignal TransductionXenograft Model Antitumor AssaysConceptsNon-small cell lung cancerEGFR inhibitor resistanceΒ-blockersInhibitor resistanceStress hormonesLiver kinase B1Epidermal growth factor receptor tyrosine kinase inhibitor resistanceLower IL-6 concentrationsΒ-blocker useIL-6 concentrationsIL-6 inhibitionCell lung cancerTyrosine kinase inhibitor resistanceEGFR-TKI resistanceInterleukin-6 expressionKinase inhibitor resistanceChronic stress hormonesNSCLC patientsEGFR-TKIIL-6Lung cancerAR activationWorse outcomesNSCLC cellsTKI resistance
2007
KRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer
Massarelli E, Varella-Garcia M, Tang X, Xavier AC, Ozburn NC, Liu DD, Bekele BN, Herbst RS, Wistuba II. KRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer. Clinical Cancer Research 2007, 13: 2890-2896. PMID: 17504988, DOI: 10.1158/1078-0432.ccr-06-3043.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungDisease ProgressionDrug Resistance, NeoplasmErbB ReceptorsErlotinib HydrochlorideFemaleGefitinibGene DosageHumansLung NeoplasmsMaleMiddle AgedMutationPrognosisProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsTreatment OutcomeConceptsEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsCell lung cancerKRAS mutationsTyrosine kinase inhibitorsEGFR-TKIEGFR copy numberEGFR mutationsLung cancerFavorable responseKinase inhibitorsShorter median timeArchival tissue specimensEGFR gene mutationsPanel of markersAdvanced NSCLCObjective responseProgressive diseaseSurvival benefitMedian timePoor responseSuch therapyDisease progressionPatients
2006
Independent review of fatal interstitial lung disease (ILD) in TRIBUTE: paclitaxel + carboplatin ± erlotinib in advanced non-small cell lung cancer (NSCLC)
Gandara D, Yoneda K, Shelton D, Beckett L, Ramies D, Bloss J, Herbst R. Independent review of fatal interstitial lung disease (ILD) in TRIBUTE: paclitaxel + carboplatin ± erlotinib in advanced non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2006, 24: 7071-7071. DOI: 10.1200/jco.2006.24.18_suppl.7071.Peer-Reviewed Original ResearchNon-small cell lung cancerInterstitial lung diseaseFatal interstitial lung diseaseRisk of ILDConcurrent illnessStudy armsEGFR-TKIILD casesRisk factorsProgressive non-small cell lung cancerAdvanced non-small cell lung cancerIncidence of ILDEGFR tyrosine kinase inhibitor therapyTyrosine kinase inhibitor therapyCell lung cancerKinase inhibitor therapyIndependent blinded assessmentConcurrent chemotherapyErlotinib armInhibitor therapyMedical oncologistsSerious complicationsOverall incidenceAsian patientsLung disease
2004
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Does Not Improve Paclitaxel Effect in an Orthotopic Mouse Model of Lung Cancer
Onn A, Isobe T, Wu W, Itasaka S, Shintani T, Shibuya K, Kenji Y, O’Reilly M, Fidler IJ, Herbst RS. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Does Not Improve Paclitaxel Effect in an Orthotopic Mouse Model of Lung Cancer. Clinical Cancer Research 2004, 10: 8613-8619. PMID: 15623645, DOI: 10.1158/1078-0432.ccr-04-1241.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, Bronchiolo-AlveolarAnimalsAntineoplastic Agents, PhytogenicCarcinoma, Non-Small-Cell LungDrug Therapy, CombinationEnzyme ActivationEnzyme InhibitorsErbB ReceptorsFibroblast Growth Factor 2HumansLung NeoplasmsMaleMiceMice, NudeMitogen-Activated Protein KinasesModels, AnimalPaclitaxelPhosphorylationPyrimidinesPyrrolesSurvival RateConceptsEGFR tyrosine kinase inhibitorsTumor implantationLung cancerKinase inhibitorsEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsBasic fibroblast growth factor expressionCombination of paclitaxelFibroblast growth factor expressionGroups of miceLungs of miceOrthotopic mouse modelHuman lung cancerTyrosine kinase inhibitorsGrowth factor expressionMaximal therapeutic effectHuman lung adenocarcinoma cellsLung adenocarcinoma cellsPaclitaxel 100Phosphorylation of EGFRConcurrent administrationEGFR-TKITherapeutic effectEpidermal growth factor receptor (EGFR) activation