2024
Lifileucel, an Autologous Tumor-infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors
Schoenfeld A, Lee S, de Speville B, Gettinger S, Hafliger S, Sukari A, Papa S, Rodríguez-Moreno J, Finckenstein F, Fiaz R, Catlett M, Chen G, Qi R, Masteller E, Gontcharova V, He K. Lifileucel, an Autologous Tumor-infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors. Cancer Discovery 2024, 14: 1389-1402. PMID: 38563600, PMCID: PMC11294887, DOI: 10.1158/2159-8290.cd-23-1334.Peer-Reviewed Original ResearchMetastatic non-small cell lung cancerAdverse eventsResistance to immune checkpoint inhibitorsPD-L1-negative tumorsPhase 2 multicenter studyLow tumor mutational burdenTreatment-emergent adverse eventsNon-small cell lung cancerTime of data cutoffRefractory to prior therapyPD-L1-negativeImmune checkpoint inhibitorsResistance to immunotherapyTumor mutational burdenCell lung cancerMultiple organ failurePotential treatment optionCheckpoint inhibitorsPrior therapyData cutoffPatient diedSystemic therapyMutational burdenSTK11 mutationsCardiac failure
2022
Brief Report: Safety and Antitumor Activity of Alectinib Plus Atezolizumab From a Phase 1b Study in Advanced ALK-Positive NSCLC
Kim DW, Gadgeel S, Gettinger SN, Riely GJ, Oxnard GR, Mekhail T, Schmid P, Dowlati A, Heist RS, Wozniak AJ, Singh J, Cha E, Spahn J, Ou SI. Brief Report: Safety and Antitumor Activity of Alectinib Plus Atezolizumab From a Phase 1b Study in Advanced ALK-Positive NSCLC. JTO Clinical And Research Reports 2022, 3: 100367. PMID: 35875467, PMCID: PMC9304608, DOI: 10.1016/j.jtocrr.2022.100367.Peer-Reviewed Original ResearchTreatment-related adverse eventsPhase 1b studyAdverse eventsPositive NSCLCAntitumor activityGrade 3 treatment-related adverse eventsPreferred first-line treatment optionAdvanced ALK-positive NSCLCMedian progression-free survivalStage IIIB/IVFirst-line treatment optionDose of alectinibIIIB/IVImmune checkpoint inhibitorsMedian overall survivalObjective response rateProgression-free survivalDose-limiting toxicityALK-positive NSCLCAtezolizumab 1200Checkpoint inhibitorsStarting doseMedian durationOverall survivalCombination regimens
2021
Prolonged Complete Response of Early Stage Primary Adenocarcinoma of the Lung to Nivolumab Monotherapy.
Unlu S, Grant MJ, Gettinger S, Adeniran A, Kluger HM. Prolonged Complete Response of Early Stage Primary Adenocarcinoma of the Lung to Nivolumab Monotherapy. Clinical Oncology Case Reports 2021, 4 PMID: 34382032, PMCID: PMC8353529.Peer-Reviewed Original ResearchMultiple primary malignant tumorsNivolumab monotherapyCheckpoint inhibitorsLung cancerHigh Programmed-Death Ligand 1 (PD-L1) expressionProgrammed Death Ligand 1 ExpressionNon-small cell lung cancerMultiple regional lymph nodesImmune checkpoint inhibitorsPD-1 inhibitorsLigand 1 expressionPrimary lung cancerEarly-stage diseaseRegional lymph nodesCell lung cancerPrimary malignant tumorsHigh-risk natureSystemic immunotherapyDurable responsesAdvanced melanomaComplete responseEffective immunotherapyLymph nodesMore patientsPrimary adenocarcinoma
2020
Immune Checkpoint Inhibitors in Thoracic Malignancies: Review of the Existing Evidence by an IASLC Expert Panel and Recommendations
Remon J, Passiglia F, Ahn MJ, Barlesi F, Forde PM, Garon EB, Gettinger S, Goldberg SB, Herbst RS, Horn L, Kubota K, Lu S, Mezquita L, Paz-Ares L, Popat S, Schalper KA, Skoulidis F, Reck M, Adjei AA, Scagliotti GV. Immune Checkpoint Inhibitors in Thoracic Malignancies: Review of the Existing Evidence by an IASLC Expert Panel and Recommendations. Journal Of Thoracic Oncology 2020, 15: 914-947. PMID: 32179179, DOI: 10.1016/j.jtho.2020.03.006.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsThoracic malignanciesCheckpoint inhibitorsThymic carcinomaDeath ligand 1 (PD-L1) immune checkpoint inhibitorsAnti-programmed cell death protein 1Cell death protein 1/T-lymphocyte antigen 4 antibodyCombination of ICIsDeath protein 1/Long-term survival benefitHost antitumor immune responseCell death protein 1Immune evasion processStage III NSCLCAntitumor immune responseEarly-stage diseaseDeath protein 1Portion of patientsMalignant pleural mesotheliomaOptimal treatment durationFuture treatment strategiesDefinitive clinical benefitFuture therapeutic developmentAvailable scientific evidence
2019
A phase II study of autologous tumor infiltrating lymphocytes (TIL, LN-144/LN-145) in patients with solid tumors.
Chesney J, Lutzky J, Thomas S, Nieva J, Munoz Couselo E, Martin-Liberal J, Rodriguez-Moreno J, Cacovean A, Li H, Fardis M, Gettinger S. A phase II study of autologous tumor infiltrating lymphocytes (TIL, LN-144/LN-145) in patients with solid tumors. Journal Of Clinical Oncology 2019, 37: tps2648-tps2648. DOI: 10.1200/jco.2019.37.15_suppl.tps2648.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsPrior immune checkpoint inhibitorsObjective response rateTIL therapyAdoptive cell therapySystemic therapyCohort 1Cohort 3RECIST 1.1Metastatic melanomaNeck cancerPhase 2 multicenterPrior systemic therapyDurable complete responseOpen-label studyPhase II studyMetastatic melanoma patientsCo-primary endpointsHigh mutational burdenAutologous tumorECOG PSMeasurable diseaseAcceptable toxicityCheckpoint inhibitorsImmunogenic tumorsEGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer
Hastings K, Yu HA, Wei W, Sanchez-Vega F, DeVeaux M, Choi J, Rizvi H, Lisberg A, Truini A, Lydon CA, Liu Z, Henick BS, Wurtz A, Cai G, Plodkowski AJ, Long NM, Halpenny DF, Killam J, Oliva I, Schultz N, Riely GJ, Arcila ME, Ladanyi M, Zelterman D, Herbst RS, Goldberg SB, Awad MM, Garon EB, Gettinger S, Hellmann MD, Politi K. EGFR mutation subtypes and response to immune checkpoint blockade treatment in non-small-cell lung cancer. Annals Of Oncology 2019, 30: 1311-1320. PMID: 31086949, PMCID: PMC6683857, DOI: 10.1093/annonc/mdz141.Peer-Reviewed Original ResearchMeSH KeywordsAgedAllelesAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmErbB ReceptorsFemaleGenetic HeterogeneityHumansLungLung NeoplasmsMaleMiddle AgedMutationProgrammed Cell Death 1 ReceptorProgression-Free SurvivalRetrospective StudiesTobacco SmokingConceptsEGFR-mutant tumorsMemorial Sloan-Kettering Cancer CenterYale Cancer CenterImmune checkpoint inhibitorsPD-L1 expressionImmune checkpoint blockadeTumor mutation burdenCancer CenterLung tumorsCheckpoint blockadeEGFR mutant lung tumorsMutant tumorsCheckpoint inhibitorsLung cancerMutation burdenImmune checkpoint blockade treatmentLow tumor mutation burdenDana-Farber Cancer InstituteEGFR wild-type lung cancersCheckpoint blockade treatmentCell lung cancerEGFR mutation subtypesSimilar smoking historyCell death 1Lung cancer casesIncidence of pancreatitis with the use of immune checkpoint inhibitors (ICI) in advanced cancers: A systematic review and meta-analysis
George J, Bajaj D, Sankaramangalam K, Yoo JW, Joshi NS, Gettinger S, Price C, Farrell JJ. Incidence of pancreatitis with the use of immune checkpoint inhibitors (ICI) in advanced cancers: A systematic review and meta-analysis. Pancreatology 2019, 19: 587-594. PMID: 31076344, DOI: 10.1016/j.pan.2019.04.015.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsIncidence of pancreatitisImmune side effectsPD-1 inhibitorsLipase elevationCheckpoint inhibitorsClinical trialsSide effectsSystematic reviewCTLA-4 agentsGrade 2 pancreatitisCTLA-4 inhibitorsLong-term complicationsNon-melanoma cancersICI combinationsICI useTerm complicationsAdvanced cancerTrue incidenceCTLA-4Appropriate treatmentPancreatitisSolid tumorsTumor typesPatientsImmune Checkpoint Inhibitor–Associated Pericarditis
Altan M, Toki MI, Gettinger SN, Carvajal-Hausdorf DE, Zugazagoitia J, Sinard JH, Herbst RS, Rimm DL. Immune Checkpoint Inhibitor–Associated Pericarditis. Journal Of Thoracic Oncology 2019, 14: 1102-1108. PMID: 30851443, PMCID: PMC6617516, DOI: 10.1016/j.jtho.2019.02.026.Peer-Reviewed Original ResearchConceptsAdverse eventsCTLA-4 inhibitorsImmune checkpoint inhibitorsDeath-1/Pericardial window procedureCheckpoint inhibitorsThird patientClinical presentationCardiac toxicityHistopathologic findingsSide effectsPericarditisPatientsDeath ligandsPotential mechanismsWindow procedureInhibitorsImmunotherapyNSCLCCardiotoxicityAutopsiesTherapy
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 outcomesCryotherapy for nodal metastasis in NSCLC with acquired resistance to immunotherapy
Adam LC, Raja J, Ludwig JM, Adeniran A, Gettinger SN, Kim HS. Cryotherapy for nodal metastasis in NSCLC with acquired resistance to immunotherapy. Journal For ImmunoTherapy Of Cancer 2018, 6: 147. PMID: 30541627, PMCID: PMC6292083, DOI: 10.1186/s40425-018-0468-x.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerMetastatic diseaseNodal metastasisLung cancerMetastatic non-small cell lung cancerDurable complete responseLymph nodal metastasisMalignant pericardial effusionCervical lymph nodesPD-L1 expressionSquamous cell cancerImmune checkpoint immunotherapyLong-term effectivenessCombination immunotherapyCheckpoint inhibitorsPericardial effusionCheckpoint immunotherapyComplete responseLymph nodesCell cancerFemale smokersLung lesionsResistant metastasesConventional chemotherapyOncolytic virus immunotherapy: future prospects for oncology
Raja J, Ludwig JM, Gettinger SN, Schalper KA, Kim HS. Oncolytic virus immunotherapy: future prospects for oncology. Journal For ImmunoTherapy Of Cancer 2018, 6: 140. PMID: 30514385, PMCID: PMC6280382, DOI: 10.1186/s40425-018-0458-z.Peer-Reviewed Original ResearchConceptsOncolytic virusesSevere immune-related adverse eventsImmune-related adverse eventsAnti-tumor immune responseEarly-stage clinical trialsImmune checkpoint inhibitorsSerious adverse effectsOncolytic viral therapyLimited therapeutic responseAnti-cancer treatmentLocal target cellsCheckpoint inhibitorsSalvage therapyTolerability profileCytotoxic chemotherapyAdverse eventsImmune dysregulationOncologic careTherapeutic optionsTumor bedSuch therapyTherapeutic responseClinical trialsNovel therapiesViral therapyDifferential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti–PD-L1)
Kowanetz M, Zou W, Gettinger SN, Koeppen H, Kockx M, Schmid P, Kadel EE, Wistuba I, Chaft J, Rizvi NA, Spigel DR, Spira A, Hirsch FR, Cohen V, Smith D, Boyd Z, Miley N, Flynn S, Leveque V, Shames DS, Ballinger M, Mocci S, Shankar G, Funke R, Hampton G, Sandler A, Amler L, Mellman I, Chen DS, Hegde PS. Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti–PD-L1). Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e10119-e10126. PMID: 30297397, PMCID: PMC6205493, DOI: 10.1073/pnas.1802166115.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-L1 expressionImmune cellsTumor cellsCases of NSCLCHigh PD-L1 expressionHigh PD-L1 levelsSingle-agent checkpoint inhibitorsAntitumor T-cell responsesTumor-infiltrating immune cellsPD-L1 levelsEffector T cellsTumor-infiltrating lymphocytesDurable clinical responsesPD-L1 geneT cell responsesCell lung cancerStratification of patientsPoor immune infiltrationCheckpoint inhibitorsClinical responseAnticancer immunityImmune infiltrationLung cancerDesmoplastic stromaCollateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors
Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H, Weiss SA, Gettinger S, Sznol M, Young A, Rushakoff R, Lee J, Bluestone JA, Anderson M, Herold KC. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes 2018, 67: dbi180002. PMID: 29937434, PMCID: PMC6054443, DOI: 10.2337/dbi18-0002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, ImmunologicalAutoimmune DiseasesB7-H1 AntigenDiabetes Mellitus, Type 1Genetic Predisposition to DiseaseGenotypeHLA-DR4 AntigenHumansHypoglycemic AgentsInsulinInsulin SecretionIsoantibodiesKetosisModels, ImmunologicalNeoplasmsPancreasPancreatitisProgrammed Cell Death 1 ReceptorConceptsInsulin-dependent diabetesCheckpoint inhibitorsAdverse eventsHLA-DR4Classic type 1 diabetesPD-L1 checkpoint inhibitorsEvidence of pancreatitisImmune adverse eventsSolid organ cancersType 1 diabetesPeridiagnosis periodPositive autoantibodiesL1 antibodyInsulin-DependentHigh riskPatientsDiabetesCancerInhibitorsKetoacidosisAutoimmuneAutoantibodiesPancreatitisComplicationsSyndromeEarly Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA
Goldberg SB, Narayan A, Kole AJ, Decker RH, Teysir J, Carriero NJ, Lee A, Nemati R, Nath SK, Mane SM, Deng Y, Sukumar N, Zelterman D, Boffa DJ, Politi K, Gettinger S, Wilson LD, Herbst RS, Patel AA. Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA. Clinical Cancer Research 2018, 24: 1872-1880. PMID: 29330207, PMCID: PMC5899677, DOI: 10.1158/1078-0432.ccr-17-1341.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsCtDNA responseCheckpoint inhibitorsCtDNA levelsMetastatic non-small cell lung cancerImmune checkpoint inhibitor therapySuperior progression-free survivalRadiographic tumor sizeCheckpoint inhibitor therapyProgression-free survivalSuperior overall survivalTumor DNA levelsCell lung cancerAllele fractionClin Cancer ResMultigene next-generation sequencingMutant allele fractionTumor cell deathInhibitor therapyOverall survivalRadiographic responseImmunotherapy efficacyImmunotherapy responseMedian timeNivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases
Vokes EE, Ready N, Felip E, Horn L, Burgio MA, Antonia SJ, Frontera O, Gettinger S, Holgado E, Spigel D, Waterhouse D, Domine M, Garassino M, Chow LQM, Blumenschein G, Barlesi F, Coudert B, Gainor J, Arrieta O, Brahmer J, Butts C, Steins M, Geese WJ, Li A, Healey D, Crinò L. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Annals Of Oncology 2018, 29: 959-965. PMID: 29408986, DOI: 10.1093/annonc/mdy041.Peer-Reviewed Original ResearchConceptsBaseline liver metastasesImproved overall survivalLiver metastasesCell lung cancerOverall survivalOS benefitCheckMate 017Nonsquamous NSCLCLung cancerSubgroup analysisAnti-programmed death-1 (PD-1) antibody nivolumabNivolumab-treated patientsImmune checkpoint inhibitorsPrimary end pointHepatic adverse eventsPhase III trialsFavorable safety profileNew safety concernsCheckMate 057Advanced NSCLCCheckpoint inhibitorsAdverse eventsIII trialsOS ratesAntibody nivolumab
2017
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer. Cancer Discovery 2017, 7: cd-17-0593. PMID: 29025772, PMCID: PMC5718941, DOI: 10.1158/2159-8290.cd-17-0593.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPatient-derived xenograftsHLA class ILung cancerClass ICell surface HLA class ILung cancer mouse modelPD-1 blockadeStandard treatment algorithmCancer mouse modelLung cancer samplesDefective antigen processingCheckpoint inhibitorsPD-1Treatment algorithmMouse modelAntagonistic antibodiesDiverse malignanciesAntigen processingCancer samplesB2MHomozygous lossTumorsCancerRecurrent mutations
2016
Association of Acute Interstitial Nephritis With Programmed Cell Death 1 Inhibitor Therapy in Lung Cancer Patients
Shirali AC, Perazella MA, Gettinger S. Association of Acute Interstitial Nephritis With Programmed Cell Death 1 Inhibitor Therapy in Lung Cancer Patients. American Journal Of Kidney Diseases 2016, 68: 287-291. PMID: 27113507, DOI: 10.1053/j.ajkd.2016.02.057.Peer-Reviewed Original ResearchConceptsAcute interstitial nephritisPD-1 inhibitor therapyInhibitor therapyInterstitial nephritisLung cancerNon-small cell lung cancerAnti-PD-1 antibodyAcute kidney injuryImmune checkpoint inhibitorsT cell immunityCell lung cancerLung cancer patientsClinical trial dataRenal toleranceCheckpoint inhibitorsKidney injuryDeath-1Kidney biopsyCancer patientsPatientsTrial dataTherapyAdverse effectsDrugsNephritis