2023
Safety and clinical activity of atezolizumab plus erlotinib in patients with non-small-cell lung cancer
Rudin C, Cervantes A, Dowlati A, Besse B, Ma B, Costa D, Schmid P, Heist R, Villaflor V, Spahn J, Li S, Cha E, Riely G, Gettinger S. Safety and clinical activity of atezolizumab plus erlotinib in patients with non-small-cell lung cancer. ESMO Open 2023, 8: 101160. PMID: 36871392, PMCID: PMC10163154, DOI: 10.1016/j.esmoop.2023.101160.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntibodies, Monoclonal, HumanizedCarcinoma, Non-Small-Cell LungErlotinib HydrochlorideHumansLung NeoplasmsConceptsTreatment-related adverse eventsCell lung cancerAdverse eventsLung cancerClinical activityEpidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) efficacyGrade 3 treatment-related adverse eventsEGFR TKI-naive patientsMedian progression-free survivalEGFR mutation-positive NSCLCAdvanced EGFR mutation-positive NSCLCTyrosine kinase inhibitor efficacyDurable clinical activityTolerable safety profileMedian overall survivalMedian response durationObjective response ratePhase Ib trialSerious adverse eventsProgression-free survivalStage 2 patientsMutation-positive NSCLCEGFR-mutant NSCLCTKI-naive patientsAtezolizumab 1200
2019
The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma
Truini A, Starrett JH, Stewart T, Ashtekar K, Walther Z, Wurtz A, Lu D, Park JH, DeVeaux M, Song X, Gettinger S, Zelterman D, Lemmon MA, Goldberg SB, Politi K. The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma. Clinical Cancer Research 2019, 25: 6382-6391. PMID: 31182434, PMCID: PMC6825535, DOI: 10.1158/1078-0432.ccr-19-0780.Peer-Reviewed Original Research
2018
Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC
Gettinger S, Hellmann MD, Chow LQM, Borghaei H, Antonia S, Brahmer JR, Goldman JW, Gerber DE, Juergens RA, Shepherd FA, Laurie SA, Young TC, Li X, Geese WJ, Rizvi N. Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. Journal Of Thoracic Oncology 2018, 13: 1363-1372. PMID: 29802888, DOI: 10.1016/j.jtho.2018.05.015.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCarcinoma, Non-Small-Cell LungErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMiddle AgedNivolumabConceptsAdvanced EGFR-mutant NSCLCEGFR-mutant NSCLCTreatment-related grade 3 toxicitiesEGFR-mutant advanced NSCLCProgression-free survival ratesEGFR T790M mutationEGFR tyrosine kinase inhibitorsGrade 3 toxicityObjective response rateTKI-naive patientsCompound EGFR mutationsT790M mutationTyrosine kinase inhibitorsImmune-related responsesInvestigator recordsAdvanced NSCLCDurable responsesUnacceptable toxicityComplete responseFourth patientDisease progressionEGFR mutationsMutant NSCLCTumor biopsiesNivolumab
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 cohortA phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer
Wakelee HA, Gettinger S, Engelman J, Jänne PA, West H, Subramaniam DS, Leach J, Wax M, Yaron Y, Miles DR, Lara PN. A phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer. Cancer Chemotherapy And Pharmacology 2017, 79: 923-932. PMID: 28352985, PMCID: PMC5403837, DOI: 10.1007/s00280-017-3283-z.Peer-Reviewed Original ResearchConceptsObjective response ratePhase Ib/II studyII studyPhase INon-small cell lung cancerFrequent dose-limiting toxicityPhase IIDose of cabozantinibDose-limiting toxicityResultsSixty-four patientsCell lung cancerMulti-kinase inhibitorProgressive NSCLCStable diseaseCombination armPartial responseFrequent AEsErlotinib treatmentLung cancerEGFR mutationsErlotinib pharmacokineticsCabozantinibPatientsPrimary objectiveResponse rateManagement of Brain Metastases in Tyrosine Kinase Inhibitor–Naïve Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis
Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, Beal K, Amini A, Patil T, Kavanagh BD, Camidge DR, Braunstein SE, Boreta LC, Balasubramanian SK, Ahluwalia MS, Rana NG, Attia A, Gettinger SN, Contessa JN, Yu JB, Chiang VL. Management of Brain Metastases in Tyrosine Kinase Inhibitor–Naïve Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis. Journal Of Clinical Oncology 2017, 35: jco.2016.69.714. PMID: 28113019, DOI: 10.1200/jco.2016.69.7144.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic AgentsBrain NeoplasmsCarcinoma, Non-Small-Cell LungCombined Modality TherapyCranial IrradiationDisease-Free SurvivalErbB ReceptorsErlotinib HydrochlorideFemaleHumansLung NeoplasmsMaleMiddle AgedProtein Kinase InhibitorsRadiosurgeryRetrospective StudiesSalvage TherapySurvival RateConceptsWhole brain radiotherapyMulti-institutional analysisEGFR-mutant NSCLCBrain metastasesEGFR-TKIStereotactic radiosurgeryTyrosine kinase inhibitorsOverall survivalEpidermal growth factor receptorGrowth factor receptorIntracranial progressionLung cancerMutant non-small cell lung cancerEGFR-TKI resistance mutationNon-small cell lung cancerIntracranial progression-free survivalRetrospective multi-institutional analysisDeferral of radiotherapyEGFR-TKI useSimilar prognostic featuresUpfront EGFR-TKIProgression-free survivalFactor receptorInferior overall survivalCell lung cancer
2014
Reduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer
de Bruin EC, Cowell C, Warne PH, Jiang M, Saunders RE, Melnick MA, Gettinger S, Walther Z, Wurtz A, Heynen GJ, Heideman DA, Gómez-Román J, García-Castaño A, Gong Y, Ladanyi M, Varmus H, Bernards R, Smit EF, Politi K, Downward J. Reduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer. Cancer Discovery 2014, 4: 606-619. PMID: 24535670, PMCID: PMC4011693, DOI: 10.1158/2159-8290.cd-13-0741.Peer-Reviewed Original ResearchConceptsLung cancerMAP-ERK kinase (MEK) inhibitorsEGF receptorEGFR-mutant lung adenocarcinomaKinase inhibitorsHuman lung cancer cell linesResistance of lungSubgroup of patientsLung cancer cell linesCancer cell linesClinical responsivenessCombination therapyEGFR-TKIEGFR mutationsErlotinib resistanceLung adenocarcinomaRAS-ERK signalingEGFR inhibitionMEK inhibitorsErlotinibReduced expressionNF1 expressionPatientsCell linesNeurofibromin levels
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