2024
Treatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer After Progression on Osimertinib
Robinson N, Canavan M, Zhan P, Udelsman B, Pathak R, Boffa D, Goldberg S. Treatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer After Progression on Osimertinib. Clinical Lung Cancer 2024, 26: 9-17.e3. PMID: 39462746, DOI: 10.1016/j.cllc.2024.09.006.Peer-Reviewed Original ResearchNon-small cell lung cancerEGFR-mutant non-small cell lung cancerFirst-line osimertinibContinuation of osimertinibImmune checkpoint inhibitorsTyrosine kinase inhibitorsCell lung cancerRetrospective cohort studyOverall survivalTreatment regimensLung cancerAdvanced epidermal growth factor receptorAssociated with increased PFSAssociated with superior PFSSecond-line treatment regimenEGFR exon 19 deletionRetrospective cohort study of patientsEGFR tyrosine kinase inhibitorsAssociated with prolonged survivalCohort study of patientsSecond-line treatment regimensExon 19 deletionFirst-line therapyEpidermal growth factor receptorFirst-line treatmentPhase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A
Gettinger S, Song Z, Reckamp K, Moscow J, Gray R, Wang V, McShane L, Rubinstein L, Patton D, Williams P, Hamilton S, Kong X, Tricoli J, Conley B, Arteaga C, Harris L, O'Dwyer P, Chen A, Flaherty K. Phase II Trial of Afatinib in Patients With EGFR-Mutated Solid Tumors Excluding Lung Cancer: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol A. JCO Precision Oncology 2024, 8: e2300725. PMID: 38986051, DOI: 10.1200/po.23.00725.Peer-Reviewed Original ResearchConceptsProgression-free survivalTyrosine kinase inhibitorsEGFR tyrosine kinase inhibitorsNCI-MATCHLung cancerGlioblastoma multiformeOverall survivalAdvanced non-small cell lung cancerNational Cancer Institute-Molecular AnalysisNon-small cell lung cancerEnd pointsTumor genomic testingTrial primary end pointPhase 2 trialPhase II trialSecondary end pointsPrimary end pointCell lung cancerCohort of patientsMedian OSStable diseaseAdenosquamous carcinomaProtocol therapyPartial responseArm AExecutive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer
Nagpal S, Milano M, Chiang V, Soltys S, Brackett A, Halasz L, Garg A, Sahgal A, Ahluwalia M, Tom M, Palmer J, Knisely J, Chao S, Gephart M, Wang T, Lo S, Chang E. Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer. Neuro-Oncology 2024, 26: 1195-1212. PMID: 38459978, PMCID: PMC11226873, DOI: 10.1093/neuonc/noae041.Peer-Reviewed Original ResearchNon-small cell lung cancerTyrosine kinase inhibitorsCell lung cancerCentral nervous systemAmerican Radium SocietyALK-fusionBrain metastasesAmerican Radium Society Appropriate Use CriteriaLung cancerSequence of tyrosine kinase inhibitorsALK tyrosine kinase inhibitorsTreatment of brain metastasesEGFR tyrosine kinase inhibitorsWhole-brain RTEpidermal growth factor receptorGrowth factor receptorAppropriate Use CriteriaBrain RTEGFR-mutantRadiotherapyTreatment optionsFactor receptorKinase inhibitorsNervous systemLiterature searchASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts.
Hu B, Wiesehöfer M, de Miguel F, Liu Z, Chan L, Choi J, Melnick M, Arnal Estape A, Walther Z, Zhao D, Lopez-Giraldez F, Wurtz A, Cai G, Fan R, Gettinger S, Xiao A, Yan Q, Homer R, Nguyen D, Politi K. ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts. Cancer Research 2024, 84: 1303-1319. PMID: 38359163, DOI: 10.1158/0008-5472.can-23-0438.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsPatient-derived xenograftsEGFR mutant lung cancerMutant lung cancerPre-treatment tumorsResidual diseaseDrug toleranceLung cancerResidual tumor cells in vivoEGFR mutant lung adenocarcinomaTyrosine kinase inhibitor osimertinibEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitor treatmentTumor cells in vivoMutant lung adenocarcinomaMaximal tumor regressionTranscription factor Ascl1Drug-tolerant cellsTime of maximal responseEvidence of cellsCells in vivoOsimertinib treatmentTumor regressionSingle cell transcriptional profilingTumor cellsConsolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study
Nassar A, Kim S, Aredo J, Feng J, Shepherd F, Xu C, Kaldas D, Gray J, Dilling T, Neal J, Wakelee H, Liu Y, Lin S, Abuali T, Amini A, Nie Y, Patil T, Lobachov A, Bar J, Fitzgerald B, Fujiwara Y, Marron T, Thummalapalli R, Yu H, Owen D, Sharp J, Farid S, Rocha P, Arriola E, D'Aiello A, Cheng H, Whitaker R, Parikh K, Ashara Y, Chen L, Sankar K, Harris J, Nagasaka M, Ayanambakkam A, Velazquez A, Ragavan M, Lin J, Piotrowska Z, Wilgucki M, Reuss J, Luders H, Grohe C, Baena Espinar J, Feiner E, Punekar S, Gupta S, Leal T, Kwiatkowski D, Mak R, Adib E, Naqash A, Goldberg S. Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study. Journal Of Thoracic Oncology 2024, 19: 928-940. PMID: 38278303, DOI: 10.1016/j.jtho.2024.01.012.Peer-Reviewed Original ResearchTreatment-related adverse eventsConcurrent chemoradiationConsolidation therapyConsolidation durvalumabOverall survivalEGFR-mutant non-small-cell lung cancerAny-grade TRAEsCommon Terminology Criteria for Adverse Events versionFollow-upReal-world progression-free survivalObservational cohortNon-small-cell lung cancerPatients treated with osimertinibEGFR tyrosine kinase inhibitorsMedian duration of treatmentMulticenter retrospective cohort studyMultivariate Cox regression analysisDefinitive concurrent chemoradiationInternational retrospective analysisOptimal consolidation therapySensitive EGFR mutationsTreated with durvalumabAdverse Events versionProgression-free survivalStage III NSCLC
2023
EGFR tyrosine kinase inhibitors (TKIs) versus durvalumab (durva) following concurrent chemoradiation (CRT) in unresectable EGFR-mutant non-small-cell lung cancer (NSCLC).
Nassar A, Adib E, Feng J, Aredo J, Parikh K, Harris J, Velazquez Manana A, Ragavan M, Lin J, Piotrowska Z, Fitzgerald B, Grohé C, Sankar K, Neal J, Wakelee H, Shepherd F, Herbst R, Naqash A, Goldberg S, Kim S. EGFR tyrosine kinase inhibitors (TKIs) versus durvalumab (durva) following concurrent chemoradiation (CRT) in unresectable EGFR-mutant non-small-cell lung cancer (NSCLC). Journal Of Clinical Oncology 2023, 41: 8567-8567. DOI: 10.1200/jco.2023.41.16_suppl.8567.Peer-Reviewed Original ResearchEGFR tyrosine kinase inhibitorsDisease-free survivalTyrosine kinase inhibitorsTreatment-related adverse eventsConcurrent chemoradiationOverall survivalStage IIILonger disease-free survivalMulti-institutional retrospective analysisDefinitive radiation therapyPD-L1 expressionPD-L1 statusDefinitive concurrent chemoradiationEGFR-TKI therapyPlatinum-based chemotherapyCell lung cancerEGFR-mutant NSCLCGy of radiationAdjuvant osimertinibCTCAE 5.0PACIFIC trialAdvanced NSCLCConcurrent chemotherapyBaseline characteristicsMedian duration
2022
Clinical outcomes of non-small cell lung cancer brain metastases treated with stereotactic radiosurgery and immune checkpoint inhibitors, EGFR tyrosine kinase inhibitors, chemotherapy and immune checkpoint inhibitors, or chemotherapy alone.
Dohm A, Tang J, Mills M, Liveringhouse C, Sandoval M, Perez B, Robinson T, Creelan B, Gray J, Etame A, Vogelbaum M, Forsyth P, Yu H, Oliver D, Ahmed K. Clinical outcomes of non-small cell lung cancer brain metastases treated with stereotactic radiosurgery and immune checkpoint inhibitors, EGFR tyrosine kinase inhibitors, chemotherapy and immune checkpoint inhibitors, or chemotherapy alone. Journal Of Neurosurgery 2022, 138: 1600-1607. PMID: 36681988, DOI: 10.3171/2022.9.jns221896.Peer-Reviewed Original ResearchEpidermal growth factor receptor tyrosine kinase inhibitorsImmune checkpoint inhibitorsDistant intracranial controlNon-small cell lung cancer brain metastasesCell lung cancer brain metastasesLung cancer brain metastasesCancer brain metastasesSystemic therapyBrain metastasesStereotactic radiosurgeryCheckpoint inhibitorsLocal controlGrowth factor receptor tyrosine kinase inhibitorsSingle-fraction stereotactic radiosurgeryReceptor tyrosine kinase inhibitorsEGFR tyrosine kinase inhibitorsKinase inhibitorsChemotherapy-alone groupNSCLC BM patientsNSCLC brain metastasesTyrosine kinase inhibitorsBM diagnosisIntracranial controlBM patientsOverall survivalMET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer
Yoshida R, Saigi M, Tani T, Springer B, Shibata H, Kitajima S, Mahadevan N, Campisi M, Kim W, Kobayashi Y, Thai T, Haratani K, Yamamoto Y, Sundararaman S, Knelson E, Vajdi A, Canadas I, Uppaluri R, Paweletz C, Miret J, Lizotte P, Gokhale P, Jänne P, Barbie D. MET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer. Cancer Research 2022, 82: 4079-4092. PMID: 36066413, PMCID: PMC9627131, DOI: 10.1158/0008-5472.can-22-0770.Peer-Reviewed Original ResearchConceptsEGFR-mutant lung cancerEGFR-TKI-resistant cellsThird-generation EGFR tyrosine kinase inhibitorMET-amplifiedT cell responsesPemetrexed treatmentLung cancerCD8+ T cell immunogenicityEGFR-TKI treatment failureEGFR tyrosine kinase inhibitorsInhibit T cell responsesUpregulation of CD73Humanized mouse modelTyrosine kinase inhibitorsT-cell immunogenicityCell line studiesMET amplificationEGFR-TKIsTKI resistanceTreatment failureCancer immunogenicityCD73 inhibitionT cellsPemetrexedEnhanced immunogenicity
2021
Lung Cancer Driven by BRAFG469V Mutation Is Targetable by EGFR Kinase Inhibitors
Huo K, Notsuda H, Fang Z, Liu N, Gebregiworgis T, Li Q, Pham N, Li M, Liu N, Shepherd F, Marshall C, Ikura M, Moghal N, Tsao M. Lung Cancer Driven by BRAFG469V Mutation Is Targetable by EGFR Kinase Inhibitors. Journal Of Thoracic Oncology 2021, 17: 277-288. PMID: 34648945, DOI: 10.1016/j.jtho.2021.09.008.Peer-Reviewed Original ResearchConceptsEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitorsLung cancerBRAF mutationsNon-small cell lung cancerNon-V600 BRAF mutationsPatient-derived xenograft modelsKinase inhibitorsCell lung cancerEGFR-TKI gefitinibSingle-agent vemurafenibV600E BRAF mutationRNA knockdownCell linesExpression of BRAFOff-target inhibitionCombination dabrafenibTKI gefitinibTargeted therapyLung adenocarcinomaXenograft modelEGFR kinase inhibitorsPatientsOncogenic driversBRAFPreclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs
Colclough N, Chen K, Johnström P, Strittmatter N, Yan Y, Wrigley GL, Schou M, Goodwin R, Varnäs K, Adua SJ, Zhao M, Nguyen DX, Maglennon G, Barton P, Atkinson J, Zhang L, Janefeldt A, Wilson J, Smith A, Takano A, Arakawa R, Kondrashov M, Malmquist J, Revunov E, Vazquez-Romero A, Moein MM, Windhorst AD, Karp NA, Finlay MRV, Ward RA, Yates JWT, Smith PD, Farde L, Cheng Z, Cross DAE. Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs. Clinical Cancer Research 2021, 27: 189-201. PMID: 33028591, DOI: 10.1158/1078-0432.ccr-19-1871.Peer-Reviewed Original ResearchConceptsBlood-brain barrier permeabilityBrain metastasesBrain penetranceBarrier permeabilityEGFR tyrosine kinase inhibitorsT790M resistance mutationMetastatic brain diseaseSubclinical brain metastasesSelective EGFR tyrosine kinase inhibitorOngoing clinical evaluationM resistance mutationTyrosine kinase inhibitorsBBB penetranceBrain tumor growthClinical efficacyEGFR-TKIEGFR-TKIsBrain penetrationClinical evaluationPreclinical comparisonPreclinical modelsPreclinical studiesCynomolgus macaquesOsimertinibTumor growth
2020
Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway
Lu Y, Liu Y, Oeck S, Zhang GJ, Schramm A, Glazer PM. Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway. Cancer Research 2020, 80: 4655-4667. PMID: 32873635, PMCID: PMC7642024, DOI: 10.1158/0008-5472.can-20-1192.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAniline CompoundsAnimalsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCell HypoxiaCell Line, TumorDrug Resistance, NeoplasmHumansLung NeoplasmsMAP Kinase Signaling SystemMiceProtein Kinase InhibitorsReceptor, Fibroblast Growth Factor, Type 1Up-RegulationXenograft Model Antitumor AssaysConceptsEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitorsEpithelial-mesenchymal transitionNon-small cell lung cancer (NSCLC) cell line H1975Fibroblast growth factor receptor 1 expressionMEK inhibitorsNSCLC cell line H1975EGFR-TKI resistanceEGFR-TKI osimertinibOverexpression of FGFR1Receptor 1 expressionEGFR-TKI sensitivityExpression of FGFR1Lung cancer cellsAttractive therapeutic strategyMAPK pathwayProapoptotic factor BimClinical efficacyConventional therapyDevelopment of resistanceEGFR mutationsSelective small molecule inhibitorsTKI resistanceKnockdown of FGFR1Therapeutic strategiesDrug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance EGFR Mutations
Starrett JH, Guernet AA, Cuomo ME, Poels KE, van Alderwerelt van Rosenburgh IK, Nagelberg A, Farnsworth D, Price KS, Khan H, Ashtekar KD, Gaefele M, Ayeni D, Stewart TF, Kuhlmann A, Kaech S, Unni AM, Homer R, Lockwood WW, Michor F, Goldberg SB, Lemmon MA, Smith PD, Cross D, Politi K. Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance EGFR Mutations. Cancer Research 2020, 80: 2017-2030. PMID: 32193290, PMCID: PMC7392201, DOI: 10.1158/0008-5472.can-19-3819.Peer-Reviewed Original ResearchConceptsOsimertinib resistancePreferred first-line therapyThird-generation EGFR tyrosine kinase inhibitorEGFR tyrosine kinase inhibitorsResistance EGFR mutationsFirst-line therapyMutant lung cancerFirst-line osimertinibSubsequent treatment approachesTransgenic mouse modelTyrosine kinase inhibitorsSecondary mutationsErlotinib treatmentLung cancerEGFR mutationsLung adenocarcinomaMouse modelTherapeutic strategiesTherapeutic testingTreatment approachesMutant tumorsResistance mutationsDrug sensitivityDriver mutationsKinase inhibitors
2019
1450P Frequency of epidermal growth factor receptor (EGFR) mutations in stage IB–IIIA EGFR mutation positive non-small cell lung cancer (NSCLC) after complete tumour resection
Tsuboi M, Herbst R, John T, Grohe C, Majem M, Goldman J, Kim S, Yu C, Miziara J, Novello S, Urban D, Akewanlop C, Öztürk A, Quang B, Kowalski D, Marmol D, Marotti M, Laus G, Wu Y. 1450P Frequency of epidermal growth factor receptor (EGFR) mutations in stage IB–IIIA EGFR mutation positive non-small cell lung cancer (NSCLC) after complete tumour resection. Annals Of Oncology 2019, 30: v589. DOI: 10.1093/annonc/mdz258.010.Peer-Reviewed Original ResearchNon-small cell lung cancerBristol-Myers SquibbComplete tumor resectionEGFR mutationsBoehringer IngelheimMerck SharpAdjuvant therapyComplete resectionTumor resectionStage IB-IIIA non-small cell lung cancerEGFRm non-small cell lung cancerMutation-positive non-small cell lung cancerEarly-stage non-small cell lung cancerEGFR mutation-positive non-small cell lung cancerEli LillyOral EGFR tyrosine kinase inhibitorPositive non-small cell lung cancerT790MEpidermal growth factor receptor (EGFR) mutationsEGFR T790M mutationEGFR tyrosine kinase inhibitorsGenentech/RocheNon-squamous histologySafety of osimertinibPlacebo-controlled studyInvestigating racial differences in treatment responses through analysis of real-world data (RWD).
Liu Z, Ma M, Grover K, Li L, Goldsweig H, Yadav K, Zhou X, Mullaney T, Redfern A, Jappe W, Zimmerman M, Prentice T, Pan Q, Oh W, Schadt E, Li D, Chen R. Investigating racial differences in treatment responses through analysis of real-world data (RWD). Journal Of Clinical Oncology 2019, 37: e18141-e18141. DOI: 10.1200/jco.2019.37.15_suppl.e18141.Peer-Reviewed Original ResearchAdvanced non-small cell lung cancerMetastatic castration-resistant prostate cancerMetastatic breast cancerMedian TTDTreatment discontinuationUnresectable hepatocellular carcinomaCheckpoint inhibitorsHepatocellular carcinomaClinical trialsTreatment responseNon-small cell lung cancerEvidence-based cancer careCastration-resistant prostate cancerTherapeutic agentsEGFR tyrosine kinase inhibitorsLonger TTDSurrogate clinical endpointsImmune checkpoint inhibitorsMetastatic colorectal cancerRace groupsCell lung cancerPost-menopausal womenEGFR antibody cetuximabClinical trial resultsWild-type KRAS
2018
EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes
Marcoux N, Gettinger SN, O’Kane G, Arbour KC, Neal JW, Husain H, Evans TL, Brahmer JR, Muzikansky A, Bonomi PD, del Prete S, Wurtz A, Farago AF, Dias-Santagata D, Mino-Kenudson M, Reckamp KL, Yu HA, Wakelee HA, Shepherd FA, Piotrowska Z, Sequist LV. EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes. Journal Of Clinical Oncology 2018, 37: 278-285. PMID: 30550363, PMCID: PMC7001776, DOI: 10.1200/jco.18.01585.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Non-Small-Cell LungClass I Phosphatidylinositol 3-KinasesErbB ReceptorsFemaleGenetic Predisposition to DiseaseHumansLung NeoplasmsMaleMiddle AgedMutationNeoplasm GradingNorth AmericaPhenotypeRetinoblastoma Binding ProteinsRetrospective StudiesSmall Cell Lung CarcinomaTime FactorsTreatment OutcomeTumor Suppressor Protein p53Ubiquitin-Protein LigasesConceptsNon-small cell lung cancerSmall cell lung cancerEGFR-mutant non-small cell lung cancerSCLC transformationLung cancerNeuroendocrine carcinomaEGFR mutationsDe novo small cell lung cancersInitial lung cancer diagnosisHigh-grade neuroendocrine carcinomaEGFR tyrosine kinase inhibitorsT790M positivityMedian overall survivalCell lung cancerTyrosine kinase inhibitorsHigh response rateEGFR-mutant adenocarcinomaLung cancer diagnosisCNS metastasesCheckpoint inhibitorsMedian survivalOverall survivalClinical courseMixed histologyClinical outcomesTargeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer
Yochum Z, Cades J, Wang H, Chatterjee S, Simons B, O’Brien J, Khetarpal S, Lemtiri-Chlieh G, Myers K, Huang E, Rudin C, Tran P, Burns T. Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer. Oncogene 2018, 38: 656-670. PMID: 30171258, PMCID: PMC6358506, DOI: 10.1038/s41388-018-0482-y.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAmino Acid SubstitutionAniline CompoundsCarcinoma, Non-Small-Cell LungCell Line, TumorDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionErbB ReceptorsHEK293 CellsHumansLung NeoplasmsMutation, MissenseNeoplasm ProteinsNuclear ProteinsPiperazinesProtein Kinase InhibitorsTwist-Related Protein 1ConceptsEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitorsEGFR-TKI resistanceGeneration EGFR tyrosine kinase inhibitorsCell lung cancerEGFR-mutant NSCLCLung cancerTKI resistanceTwist1 overexpressionFirst-generation EGFR tyrosine kinase inhibitorsThird-generation EGFR tyrosine kinase inhibitorEGFR-mutant lung cancerEGFR-mutant NSCLC cellsFirst-line settingLong-term efficacyDe novo resistanceT790M mutationErlotinib-induced apoptosisEpithelial-mesenchymal transition transcription factorsDrivers of EMTDrivers of resistanceEMT transcription factor TWIST1Osimertinib resistanceErlotinib resistanceNovo resistanceNivolumab 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 ResearchConceptsAdvanced 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
EGFR Exon 19 Deletion in Pancreatic Adenocarcinoma Responds to Erlotinib, Followed by T790M-Mediated Resistance.
Cecchini M, Sklar J, Lacy J. EGFR Exon 19 Deletion in Pancreatic Adenocarcinoma Responds to Erlotinib, Followed by T790M-Mediated Resistance. Journal Of The National Comprehensive Cancer Network 2017, 15: 1085-1089. PMID: 28874593, DOI: 10.6004/jnccn.2017.0151.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaTyrosine kinase inhibitorsMetastatic pancreatic ductal adenocarcinomaEGFR Exon 19 DeletionEGFR tyrosine kinase inhibitorsImmune checkpoint inhibitorsMetastatic pancreatic cancerExon 19 deletionsEpidermal growth factor receptorGrowth factor receptorAdvanced diseaseCheckpoint inhibitorsMultidrug chemotherapyPancreatic cancerDisease progressionDuctal adenocarcinomaPancreatic adenocarcinomaActionable mutationsTumor typesKinase inhibitorsExon 19Factor receptorAdenocarcinomaPatientsErlotinib
2016
Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial
Gettinger SN, Bazhenova LA, Langer CJ, Salgia R, Gold KA, Rosell R, Shaw AT, Weiss GJ, Tugnait M, Narasimhan NI, Dorer DJ, Kerstein D, Rivera VM, Clackson T, Haluska FG, Camidge DR. Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial. The Lancet Oncology 2016, 17: 1683-1696. PMID: 27836716, DOI: 10.1016/s1470-2045(16)30392-8.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsPhase 2 doseCell lung cancerObjective responsePrimary endpointAdvanced malignanciesAdverse eventsLung cancerGrade 3ALK inhibitorsPrevious EGFR-tyrosine kinase inhibitorsSerious treatment-emergent adverse eventsCohort 5Phase 2 primary endpointRandomised phase 2 trialPotential new treatment optionAnaplastic lymphoma kinase (ALK) gene rearrangementEGFR tyrosine kinase inhibitorsCommon grade 3Acceptable safety profilePhase 2 trialProportion of patientsTotal daily dosesPotent preclinical activityNew treatment optionsThe International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation–Positive Non–Small Cell Lung Cancer: Status in 2016
Tan DS, Yom SS, Tsao MS, Pass HI, Kelly K, Peled N, Yung RC, Wistuba II, Yatabe Y, Unger M, Mack PC, Wynes MW, Mitsudomi T, Weder W, Yankelevitz D, Herbst RS, Gandara DR, Carbone DP, Bunn PA, Mok TS, Hirsch FR. The International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation–Positive Non–Small Cell Lung Cancer: Status in 2016. Journal Of Thoracic Oncology 2016, 11: 946-963. PMID: 27229180, DOI: 10.1016/j.jtho.2016.05.008.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTyrosine kinase inhibitorsEGFR tyrosine kinase inhibitorsCell lung cancerLung cancerEpidermal growth factor receptor (EGFR) geneTreatment optionsConsensus statementEGFR-mutant non-small cell lung cancerEGFR Mutation-Positive NonFirst-line treatment optionSmall cell lung cancerThird-generation EGFR-TKI osimertinibCancer consensus statementLocal treatment optionsNew clinical algorithmEGFR-TKI osimertinibHigh response rateBrain metastasesRepeat biopsyClinical profileGrowth factor receptor geneClinical algorithmClinical guidelinesTreatment paradigm
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