2017
Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib
Horn L, Gettinger S, Camidge DR, Smit EF, Janjigian YY, Miller VA, Pao W, Freiwald M, Fan J, Wang B, Chand VK, Groen HJM. Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib. Lung Cancer 2017, 113: 51-58. PMID: 29110849, DOI: 10.1016/j.lungcan.2017.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAfatinibAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCetuximabCohort StudiesDiarrheaDisease ProgressionDrug Resistance, NeoplasmErbB ReceptorsErlotinib HydrochlorideExanthemaFemaleGefitinibHumansKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedMutationQuinazolinesConceptsEGFR mutation-positive NSCLCEpidermal growth factor receptorMutation-positive NSCLCCell lung cancerAdverse eventsAfatinib monotherapyMedian PFSLung cancerDrug-related grade 3/4 adverse eventsFrequent drug-related adverse eventsDrug-related adverse eventsGrade 3/4 adverse eventsAddition of cetuximabIntolerable adverse eventsPhase Ib trialT790M-negative tumorsPercent of patientsPredictable safety profileAfatinib dailyGrowth factor receptorIb trialSafety profileClinical activityDry skinSeparate cohort
2014
Dual Inhibition of EGFR with Afatinib and Cetuximab in Kinase Inhibitor–Resistant EGFR-Mutant Lung Cancer with and without T790M Mutations
Janjigian YY, Smit EF, Groen HJ, Horn L, Gettinger S, Camidge DR, Riely GJ, Wang B, Fu Y, Chand VK, Miller VA, Pao W. Dual Inhibition of EGFR with Afatinib and Cetuximab in Kinase Inhibitor–Resistant EGFR-Mutant Lung Cancer with and without T790M Mutations. Cancer Discovery 2014, 4: 1036-1045. PMID: 25074459, PMCID: PMC4155006, DOI: 10.1158/2159-8290.cd-14-0326.Peer-Reviewed Original ResearchConceptsEGFR-mutant lung cancerT790M mutationLung cancerM mutationGrade 3/4 adverse eventsMedian progression-free survivalEGFR T790M mutationErlotinib/gefitinibRobust clinical activityT790M-negative tumorsManageable safety profileObjective response ratePhase Ib studyProgression-free survivalMutant lung cancerGefitinib/erlotinibFirst clinical proofReversible EGFR inhibitorsAdverse eventsMedian durationObjective responseSafety profilePreclinical hypothesisEGFR mutationsClinical activityAcquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1
Pirazzoli V, Nebhan C, Song X, Wurtz A, Walther Z, Cai G, Zhao Z, Jia P, de Stanchina E, Shapiro EM, Gale M, Yin R, Horn L, Carbone DP, Stephens PJ, Miller V, Gettinger S, Pao W, Politi K. Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1. Cell Reports 2014, 7: 999-1008. PMID: 24813888, PMCID: PMC4074596, DOI: 10.1016/j.celrep.2014.04.014.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAfatinibAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCetuximabDrug Resistance, NeoplasmErbB ReceptorsHumansLung NeoplasmsMechanistic Target of Rapamycin Complex 1MiceMice, NudeMice, TransgenicMultiprotein ComplexesMutationQuinazolinesRandom AllocationTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsTyrosine kinase inhibitorsFirst-generation tyrosine kinase inhibitorEGFR-mutant lung adenocarcinomaLung adenocarcinomaMechanisms of resistanceEGFR antibody cetuximabPotential therapeutic strategyBiopsy specimensAntibody cetuximabDrug combinationsMouse modelTherapeutic strategiesAfatinibAddition of rapamycinCetuximabDual inhibitionAcquired ResistanceKinase inhibitorsGenomic alterationsAdenocarcinomaPatientsActivationGenomic mechanismsDrugsMTORC1 activation
2013
Treatment of Stage IV Non-small Cell Lung Cancer Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Socinski MA, Evans T, Gettinger S, Hensing TA, Sequist L, Ireland B, Stinchcombe TE. Treatment of Stage IV Non-small Cell Lung Cancer Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST Journal 2013, 143: e341s-e368s. PMID: 23649446, PMCID: PMC4694611, DOI: 10.1378/chest.12-2361.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Non-Small-Cell LungCetuximabErlotinib HydrochlorideGlutamatesGuanineHumansLung NeoplasmsNeoplasm StagingPatient SelectionPemetrexedPlatinum CompoundsProtein Kinase InhibitorsQuinazolinesConceptsStage IV non-small cell lung cancerNon-small cell lung cancerFirst-line therapyPerformance statusNonsquamous histologyLung cancerAmerican CollegeChest Physicians Evidence-Based Clinical Practice GuidelinesEastern Cooperative Oncology Group (ECOG) PSChest Physicians Lung Cancer GuidelinesEvidence-based clinical practice guidelinesNon-small cell lung cancer diagnosisEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsCell lung cancer diagnosisReceptor tyrosine kinase inhibitorsClinical patient characteristicsLung cancer guidelinesRole of cetuximabSafety of bevacizumabThird-line settingECOG performance statusGood performance statusPlatinum-based regimensPoor performance status
2012
Incorporating Bevacizumab and Erlotinib in the Combined-Modality Treatment of Stage III Non–Small-Cell Lung Cancer: Results of a Phase I/II Trial
Socinski MA, Stinchcombe TE, Moore DT, Gettinger SN, Decker RH, Petty WJ, Blackstock AW, Schwartz G, Lankford S, Khandani A, Morris DE. Incorporating Bevacizumab and Erlotinib in the Combined-Modality Treatment of Stage III Non–Small-Cell Lung Cancer: Results of a Phase I/II Trial. Journal Of Clinical Oncology 2012, 30: 3953-3959. PMID: 23045594, DOI: 10.1200/jco.2012.41.9820.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabCarcinoma, Non-Small-Cell LungChemotherapy, AdjuvantDisease-Free SurvivalDrug Administration ScheduleErlotinib HydrochlorideEsophagitisEsophagusFemaleHumansKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedNeoplasm StagingQuinazolinesRadiotherapy, ConformalRemission InductionTracheoesophageal FistulaTreatment FailureConceptsPhase I/II trialCell lung cancerConsolidation therapyII trialLung cancerObjective response rateUse of bevacizumabPhase I portionStage III NSCLCCombined modality treatmentOverall survival timeConformal radiation therapyEsophageal toxicityConcurrent chemoradiotherapyConcurrent chemotherapyEligible patientsInduction chemotherapyPrincipal toxicityEfficacy signalsCohort 2Cohort 1I portionBevacizumabRadiation therapySurvival time
2011
Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors
Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, Akhavanfard S, Heist RS, Temel J, Christensen JG, Wain JC, Lynch TJ, Vernovsky K, Mark EJ, Lanuti M, Iafrate AJ, Mino-Kenudson M, Engelman JA. Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors. Science Translational Medicine 2011, 3: 75ra26. PMID: 21430269, PMCID: PMC3132801, DOI: 10.1126/scitranslmed.3002003.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSmall cell lung cancerCell lung cancerLung cancerEpidermal growth factor receptorEGFR mutationsDrug resistanceEGFR inhibitorsDrug-resistant non-small cell lung cancerEGFR T790M mutationEGFR tyrosine kinase inhibitorsMET gene amplificationEGFR inhibitor treatmentT790M mutationTyrosine kinase inhibitorsDrug-resistant tumorsGrowth factor receptorSerial biopsiesSCLC treatmentMechanisms of resistanceHistological evolutionResistant tumorsTumor biopsiesSuch cancersInhibitor treatment
2008
Targeted Therapy in Advanced Non-Small-Cell Lung Cancer
Gettinger S. Targeted Therapy in Advanced Non-Small-Cell Lung Cancer. Seminars In Respiratory And Critical Care Medicine 2008, 29: 291-301. PMID: 18506667, DOI: 10.1055/s-2008-1076749.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBenzenesulfonatesBevacizumabCarcinoma, Non-Small-Cell LungDrug Delivery SystemsEpidermal Growth FactorErlotinib HydrochlorideHumansIndolesLung NeoplasmsNiacinamidePhenylurea CompoundsPiperidinesProtein Kinase InhibitorsPyridinesPyrrolesQuinazolinesSignal TransductionSorafenibSunitinibTreatment OutcomeVascular Endothelial Growth Factor AConceptsPhase II trialLung cancerEpidermal growth factor receptorII trialEGFR inhibitorsSmall molecule inhibitorsAdvanced non-small cell lung cancerNon-small cell lung cancerStandard first-line chemotherapyVascular endothelial growth factor (VEGF) pathwayEndothelial growth factor pathwayCancer cell pathwaysStandard salvage chemotherapyFirst-line chemotherapyPhase III studyPhase III trialsCell lung cancerSignificant survival advantageEGFR gene mutationsLeast equivalent activityVEGF receptor tyrosine kinasesCancer cell proliferationGrowth factor pathwaysGrowth factor receptorSalvage chemotherapy