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 outcomesNivolumab 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
Circulating tumor DNA (ctDNA) to monitor treatment response and progression in patients treated with tyrosine kinase inhibitors (TKIs) and immunotherapy for EGFR-mutant non-small cell lung cancer (NSCLC).
Henick B, Goldberg S, Narayan A, Rossi C, Rodney S, Kole A, Politi K, Gettinger S, Herbst R, Patel A. Circulating tumor DNA (ctDNA) to monitor treatment response and progression in patients treated with tyrosine kinase inhibitors (TKIs) and immunotherapy for EGFR-mutant non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2017, 35: e20652-e20652. DOI: 10.1200/jco.2017.35.15_suppl.e20652.Peer-Reviewed Original ResearchNon-small cell lung cancerTyrosine kinase inhibitorsEGFR-mutant non-small cell lung cancerCtDNA levelsDisease progressionRadiographic progressionTKI therapyEGFR mutationsEGFR mutation-positive non-small cell lung cancerMutation-positive non-small cell lung cancerT790MAnti-PD-1 monotherapyEGFR mutation-positive patientsPD-1 inhibitor monotherapyEGFR-mutant NSCLC patientsSubset of patientsCell lung cancerMutation-positive patientsAssessment of responseLow ctDNA levelsChart reviewClinical characteristicsDurable responsesInhibitor monotherapyNSCLC patientsMET amplification (amp) as a resistance mechanism to osimertinib.
Piotrowska Z, Thress K, Mooradian M, Heist R, Azzoli C, Temel J, Rizzo C, Nagy R, Lanman R, Gettinger S, Evans T, Hata A, Shaw A, Sequist L. MET amplification (amp) as a resistance mechanism to osimertinib. Journal Of Clinical Oncology 2017, 35: 9020-9020. DOI: 10.1200/jco.2017.35.15_suppl.9020.Peer-Reviewed Original ResearchA 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 rate
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 activityReduced 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
A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer
Johung KL, Yao X, Li F, Yu JB, Gettinger SN, Goldberg S, Decker RH, Hess JA, Chiang VL, Contessa JN. A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer. Clinical Cancer Research 2013, 19: 5523-5532. PMID: 23897899, DOI: 10.1158/1078-0432.ccr-13-0836.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsCarcinoma, Non-Small-Cell LungErbB ReceptorsFemaleGenotypeHumansLung NeoplasmsMaleMiddle AgedMutationProtein Kinase InhibitorsRadiation ToleranceReceptor Protein-Tyrosine KinasesRecurrenceTranslocation, GeneticTumor BurdenConceptsNon-small cell lung cancerCell lung cancerEML4-ALK translocationGamma knife treatmentLocal controlTumor genotypeLung cancerEGFR mutationsCox proportional hazards modelDistant brain controlDistant brain recurrenceGamma knife radiotherapyEGFR kinase domain mutationsSuperior local controlField local controlKRAS mutation statusProportional hazards modelKinase domain mutationsEGF receptorMetastasis sizeBrain recurrenceBrain metastasesField recurrenceClinical outcomesIndependent predictorsIdentification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma
Cai G, Wong R, Chhieng D, Levy GH, Gettinger SN, Herbst RS, Puchalski JT, Homer RJ, Hui P. Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma. Cancer Cytopathology 2013, 121: 500-507. PMID: 23495083, DOI: 10.1002/cncy.21288.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAnaplastic Lymphoma KinaseBiomarkers, TumorBone NeoplasmsCytodiagnosisDNA, NeoplasmErbB ReceptorsFeasibility StudiesFemaleGene RearrangementHumansIn Situ Hybridization, FluorescenceLiver NeoplasmsLung NeoplasmsMaleMiddle AgedMutationNeoplasm Recurrence, LocalPrognosisProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsReal-Time Polymerase Chain ReactionReceptor Protein-Tyrosine KinasesSoft Tissue NeoplasmsYoung AdultConceptsALK gene rearrangementMetastatic lung adenocarcinomaEGFR mutationsKRAS mutationsMetastatic tumorsEpidermal growth factor receptorLung adenocarcinomaCytological specimensGene rearrangementsMolecular testsMolecular alterationsKirsten rat sarcoma viral oncogene homolog (KRAS) mutationsALK gene rearrangement analysisAnaplastic lymphoma kinase (ALK) gene rearrangementEGFR T790M mutationRat sarcoma viral oncogene homolog mutationsCases of lungT790M mutationImportant therapeutic implicationsFine needle aspiratesGene rearrangement analysisCell block materialGrowth factor receptorRecurrent lungRecurrent adenocarcinoma
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