2024
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
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 A
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
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 patientsDesign of ALTA-1L (ALK in lung cancer trial of brigatinib in first-line), a randomized phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)-naive patients (pts) with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).
Tiseo M, Popat S, Gettinger S, Peters S, Haney J, Kerstein D, Camidge D. Design of ALTA-1L (ALK in lung cancer trial of brigatinib in first-line), a randomized phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)-naive patients (pts) with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2017, 35: tps9098-tps9098. DOI: 10.1200/jco.2017.35.15_suppl.tps9098.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalObjective response rateRandomized phase 3 trialPhase 3 trialPrimary endpointTKI therapyPositive non-small cell lung cancerAdvanced anaplastic lymphoma kinaseNext-generation ALK inhibitorsRandomized phase 2 trialPrior TKI therapySafety/tolerabilityPhase 1/2 trialPhase 2 trialKaplan-Meier methodCell lung cancerDuration of responseIndependent review committeeLog-rank testPotent preclinical activityTyrosine kinase inhibitorsAnaplastic lymphoma kinaseNaive patientsNSCLC ptsManagement 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
2016
1289TiP ALTA-1L (ALK in lung cancer trial of BrigAtinib in 1st Line): A randomized, phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)–naive, advanced anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC)
Popat S, Tiseo M, Gettinger S, Peters S, Haney J, Kerstein D, Camidge D. 1289TiP ALTA-1L (ALK in lung cancer trial of BrigAtinib in 1st Line): A randomized, phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)–naive, advanced anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC). Annals Of Oncology 2016, 27: vi448. DOI: 10.1093/annonc/mdw383.89.Peer-Reviewed Original ResearchCeritinib enables stereotactic radiosurgery to a previously untreatable symptomatic brain metastasis in a patient with ALK rearranged non-small cell lung cancer
Qian J, Yu J, Gettinger S, Chiang V. Ceritinib enables stereotactic radiosurgery to a previously untreatable symptomatic brain metastasis in a patient with ALK rearranged non-small cell lung cancer. Cancer Treatment And Research Communications 2016, 6: 17-19. DOI: 10.1016/j.ctrc.2016.02.002.Peer-Reviewed Original ResearchNon-small cell lung cancerAnaplastic lymphoma kinaseWhole-brain radiation therapySymptomatic brain metastasesBrain radiation therapyCell lung cancerBrain metastasesStereotactic radiosurgerySystemic therapyLung cancerRadiation therapyActive small-molecule tyrosine kinase inhibitorLarge symptomatic brain metastasisNext-generation ALK inhibitorsSmall molecule tyrosine kinase inhibitorsYear old Caucasian femaleMolecule tyrosine kinase inhibitorsGeneration ALK inhibitorsALK inhibitor crizotinibOld Caucasian femaleKey driver mutationsTyrosine kinase inhibitorsLocal therapyInhibitor crizotinibALK inhibitors
2015
Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in advanced non-squamous cell (non-SQ) non-small cell lung cancer (NSCLC).
Paz-Ares L, Horn L, Borghaei H, Spigel D, Steins M, Ready N, Chow L, Vokes E, Felip E, Holgado E, Barlesi F, Kohlhaeufl M, Rodriguez O, Burgio M, Fayette J, Gettinger S, Harbison C, Dorange C, Finckenstein F, Brahmer J. Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in advanced non-squamous cell (non-SQ) non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2015, 33: lba109-lba109. DOI: 10.1200/jco.2015.33.18_suppl.lba109.Peer-Reviewed Original ResearchNon-squamous cell non-small cell lung cancerPlatinum-based doublet chemotherapyProgression-free survivalSuperior overall survivalPD-L1 expressionOverall survivalDeath-1 immune checkpoint inhibitor antibodyInvestigator-assessed objective response rateGlobal phase III studyImmune checkpoint inhibitor antibodyNon-small cell lung cancerRandomized phase III trialCheckpoint inhibitor antibodyDrug-related AEsObjective response rateSubsequent systemic therapyTrials of nivolumabPhase III studyPhase III trialsCell lung cancerTyrosine kinase inhibitorsQuality of lifeDoublet chemotherapyIII studyIII trials
2014
1292P Alk Inhibitor Ap26113 in Patients with Advanced Malignancies, Including Alk+ Non-Small Cell Lung Cancer (Nsclc): Updated Efficacy and Safety Data
Gettinger S, Bazhenova L, Salgia R, Langer C, Gold K, Rosell R, Shaw A, Weiss G, Narasimhan N, Dorer D, Rivera V, Clackson T, Haluska F, Camidge R. 1292P Alk Inhibitor Ap26113 in Patients with Advanced Malignancies, Including Alk+ Non-Small Cell Lung Cancer (Nsclc): Updated Efficacy and Safety Data. Annals Of Oncology 2014, 25: iv455. DOI: 10.1093/annonc/mdu349.71.Peer-Reviewed Original ResearchBrain metastasesNSCLC ptsAdvanced malignanciesCommon treatment-emergent adverse eventsNon-small cell lung cancerMedian progression-free survivalTreatment-emergent adverse eventsIndependent radiological reviewProgression-free survivalCell lung cancerDuration of responseTyrosine kinase inhibitorsActive tyrosine kinase inhibitorPhase 2 portionAnti-tumor activityEvaluable ptsPrior crizotinibStable diseasePulmonary symptomsFree survivalGrade 1/2Radiological reviewAdverse eventsMulticenter studyLung cancerAcquired 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
First-in-human dose-finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies: Updated results.
Camidge D, Bazhenova L, Salgia R, Weiss G, Langer C, Shaw A, Narasimhan N, Dorer D, Rivera V, Zhang J, Clackson T, Haluska F, Gettinger S. First-in-human dose-finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies: Updated results. Journal Of Clinical Oncology 2013, 31: 8031-8031. DOI: 10.1200/jco.2013.31.15_suppl.8031.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsAdverse eventsAdvanced malignanciesCommon grade 3/4 treatment-related adverse eventsGrade 3/4 treatment-related adverse eventsEGFR-TKI resistant NSCLCNon-small cell lung cancerTreatment-related adverse eventsALK tyrosine kinase inhibitorsPhase I/IINovel tyrosine kinase inhibitorEGFR tyrosine kinase inhibitorsDose finding phaseGrade 4 dyspneaTKI-resistant NSCLCPhase II doseFollow-up scanCell lung cancerDose-finding studyAge 60 yrAnaplastic lymphoma kinaseAnti-tumor activityEpidermal growth factor receptorGrowth factor receptorStable diseaseA phase III comparative study of nivolumab (anti-PD-1; BMS-963558; ONO-4538) versus docetaxel in patients (pts) with previously treated advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC).
Gettinger S, Brahmer J, Rizvi N, Ready N, Chow L, Antonia S, Buyse M, Jassem J, Finckenstein F, Crinò L, Lynch T. A phase III comparative study of nivolumab (anti-PD-1; BMS-963558; ONO-4538) versus docetaxel in patients (pts) with previously treated advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC). Journal Of Clinical Oncology 2013, 31: tps8121-tps8121. DOI: 10.1200/jco.2013.31.15_suppl.tps8121.Peer-Reviewed Original ResearchNon-squamous NSCLCOverall survivalTyrosine kinase inhibitorsPD-L1Maintenance therapyAdvanced diseaseLung cancerDisease progressionPlatinum-based doublet chemotherapyRecurrent non-squamous NSCLCPhase III comparative studyMedian overall survivalObjective response ratePhase III studyProgression-free survivalPhase 1 studyCell lung cancerDurable antitumor activityPD-1 receptorImmune checkpoint receptorsT cell activationDoublet chemotherapyNSCLC ptsOS benefitUnacceptable toxicity
2012
1227O Activity of Afatinib/Cetuximab in Patients (PTS) with EGFR Mutant Non-Small Cell Lung Cancer (Nsclc) and Acquired Resistance (Ar) To EGFR Inhibitors
Janjigian Y, Smit E, Horn L, Groen H, Camidge D, Gettinger S, Fu Y, Denis L, Miller V, Pao W. 1227O Activity of Afatinib/Cetuximab in Patients (PTS) with EGFR Mutant Non-Small Cell Lung Cancer (Nsclc) and Acquired Resistance (Ar) To EGFR Inhibitors. Annals Of Oncology 2012, 23: ix400-ix401. DOI: 10.1016/s0923-7534(20)33838-2.Peer-Reviewed Original ResearchProgression-free survivalTyrosine kinase inhibitorsBoehringer IngelheimObjective responseClinical dataProbability of PFSMutant non-small cell lung cancerEGFR-mutant non-small cell lung cancerNon-small cell lung cancerMedian progression-free survivalEGFR T790M mutationClovis OncologyEGFR T790M testingErbB family blockerCell lung cancerEarly clinical dataCombination of afatinibEGFR-mutant NSCLCSpecific tyrosine kinase inhibitorT790M mutationUniversity Medical CenterTransgenic murine modelT790M testingEpidermal growth factor receptorEligible ptsClinical activity and safety of anti-PD1 (BMS-936558, MDX-1106) in patients with advanced non-small-cell lung cancer (NSCLC).
Brahmer J, Horn L, Antonia S, Spigel D, Gandhi L, Sequist L, Wigginton J, McDonald D, Kollia G, Gupta A, Gettinger S. Clinical activity and safety of anti-PD1 (BMS-936558, MDX-1106) in patients with advanced non-small-cell lung cancer (NSCLC). Journal Of Clinical Oncology 2012, 30: 7509-7509. DOI: 10.1200/jco.2012.30.15_suppl.7509.Peer-Reviewed Original ResearchBMS-936558Advanced NSCLCClinical activityPrior tyrosine kinase inhibitorsPrior chemotherapy regimenECOG performance statusCo-inhibitory receptorsPlatinum-based chemotherapyCell lung cancerOverall tumor burdenCycles of treatmentPercent of ptsDrug-related deathsTyrosine kinase inhibitorsActivated T cellsCohort expansionNSCLC ptsPrior therapyRECIST 1.0Chemotherapy regimenMedian durationMetastatic diseaseMultiple histologiesPerformance statusLymph nodes
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