2021
Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In VivoTumor Suppressor Genes and EGFR-Driven Lung Adenocarcinoma
Foggetti G, Li C, Cai H, Hellyer JA, Lin WY, Ayeni D, Hastings K, Choi J, Wurtz A, Andrejka L, Maghini DG, Rashleigh N, Levy S, Homer R, Gettinger SN, Diehn M, Wakelee HA, Petrov DA, Winslow MM, Politi K. Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In VivoTumor Suppressor Genes and EGFR-Driven Lung Adenocarcinoma. Cancer Discovery 2021, 11: 1736-1753. PMID: 33707235, PMCID: PMC8530463, DOI: 10.1158/2159-8290.cd-20-1385.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAdenocarcinoma of LungAniline CompoundsAnimalsAntineoplastic AgentsDisease Models, AnimalErbB ReceptorsFemaleHumansLung NeoplasmsMaleMiceConceptsSuppressor geneKey tumor suppressorPutative tumor suppressor geneTumor suppressor geneSensitivity of EGFRTumor growthOncogenic contextTumor suppressorHuman EGFRGenetic determinantsKeap1 pathwayComplex genotypesTumor suppressor gene alterationsLung cancer growthGenesDeficient lung adenocarcinomaLung adenocarcinomaGenetic alterationsIssue featureStrong driverCancer growthEGFR inhibitorsKinase inhibitorsInactivationGene alterations
2020
Brigatinib Versus Crizotinib in Advanced ALK Inhibitor–Naive ALK-Positive Non–Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial
Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, Campelo M, Kim DW, Griesinger F, Felip E, Califano R, Spira A, Gettinger SN, Tiseo M, Lin HM, Gupta N, Hanley MJ, Ni Q, Zhang P, Popat S. Brigatinib Versus Crizotinib in Advanced ALK Inhibitor–Naive ALK-Positive Non–Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial. Journal Of Clinical Oncology 2020, 38: 3592-3603. PMID: 32780660, PMCID: PMC7605398, DOI: 10.1200/jco.20.00505.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerALK-positive non-small cell lung cancerProgression-free survivalBlinded independent review committeeCell lung cancerInterim analysisLung cancerAdvanced ALK-positive non-small cell lung cancerGlobal health status/QoL scoreNext-generation anaplastic lymphoma kinase (ALK) inhibitorPositive non-small cell lung cancerPredictors of PFSPromising first-line treatmentSecond prespecified interim analysisSuperior progression-free survivalPlasma concentration-time curveAnaplastic lymphoma kinase inhibitorsPrespecified interim analysisPrimary end pointSecond interim analysisFirst-line treatmentFirst interim analysisHealth-related qualityIndependent review committeePatient-reported outcomesClinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer
Chiang AC, Sequist LVD, Gilbert J, Conkling P, Thompson D, Marcoux JP, Gettinger S, Kowanetz M, Molinero L, O'Hear C, Fassò M, Lam S, Gordon MS. Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Clinical Lung Cancer 2020, 21: 455-463.e4. PMID: 32586767, DOI: 10.1016/j.cllc.2020.05.008.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerRefractory small cell lung cancerImmune-related response criteriaTreatment-related adverse eventsProgression-free survivalOverall survivalLung cancerMedian investigator-assessed progression-free survivalGrade treatment-related adverse eventsInvestigator-assessed progression-free survivalTumor-specific T cell immunityMetastatic small cell lung cancerSolid Tumors version 1.1T-effector gene signaturePD-L1 mRNA expressionSafety of atezolizumabAntitumor activityMedian overall survivalResponse Evaluation CriteriaCohort of patientsPD-L1 signalingPhase 1 studyT cell immunityDuration of responseEligible patients
2019
NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 1.2020.
Ettinger DS, Wood DE, Aggarwal C, Aisner DL, Akerley W, Bauman JR, Bharat A, Bruno DS, Chang JY, Chirieac LR, D'Amico TA, Dilling TJ, Dobelbower M, Gettinger S, Govindan R, Gubens MA, Hennon M, Horn L, Lackner RP, Lanuti M, Leal TA, Lin J, Loo BW, Martins RG, Otterson GA, Patel SP, Reckamp KL, Riely GJ, Schild SE, Shapiro TA, Stevenson J, Swanson SJ, Tauer KW, Yang SC, Gregory K, Hughes M. NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 1.2020. Journal Of The National Comprehensive Cancer Network 2019, 17: 1464-1472. PMID: 31805526, DOI: 10.6004/jnccn.2019.0059.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungHumansImmunotherapyLung NeoplasmsPractice Guidelines as TopicComparison of Survival Rates After a Combination of Local Treatment and Systemic Therapy vs Systemic Therapy Alone for Treatment of Stage IV Non–Small Cell Lung Cancer
Uhlig J, Case MD, Blasberg JD, Boffa DJ, Chiang A, Gettinger SN, Kim HS. Comparison of Survival Rates After a Combination of Local Treatment and Systemic Therapy vs Systemic Therapy Alone for Treatment of Stage IV Non–Small Cell Lung Cancer. JAMA Network Open 2019, 2: e199702. PMID: 31433481, PMCID: PMC6707019, DOI: 10.1001/jamanetworkopen.2019.9702.Peer-Reviewed Original ResearchMeSH KeywordsAblation TechniquesAdolescentAdultAgedAged, 80 and overAntineoplastic AgentsCarcinoma, Non-Small-Cell LungChemotherapy, AdjuvantComparative Effectiveness ResearchDatabases, FactualFemaleFollow-Up StudiesHumansLung NeoplasmsMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingPneumonectomyProportional Hazards ModelsRadiotherapy, AdjuvantRetrospective StudiesSurvival RateTreatment OutcomeYoung AdultConceptsStage IV non-small cell lung cancerNon-small cell lung cancerPrimary tumor siteSuperior overall survivalSystemic therapySurgical resectionCell lung cancerExternal beam radiotherapyOverall survivalSurvival benefitLocal treatmentTumor siteTumor characteristicsLung cancerTreatment groupsMultivariable Cox proportional hazards regression modelsOligometastatic non-small cell lung cancerStage IV squamous cell carcinomaSurvival rateCox proportional hazards regression modelProportional hazards regression modelsComparative effectiveness research studyCancer-specific factorsNational Cancer DatabaseStage IV disease
2018
FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1–Selected Patients With NSCLC
Spigel DR, Chaft JE, Gettinger S, Chao BH, Dirix L, Schmid P, Chow LQM, Hicks RJ, Leon L, Fredrickson J, Kowanetz M, Sandler A, Funke R, Rizvi NA. FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1–Selected Patients With NSCLC. Journal Of Thoracic Oncology 2018, 13: 1733-1742. PMID: 29775807, PMCID: PMC7455890, DOI: 10.1016/j.jtho.2018.05.004.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsObjective response ratePD-L1 expressionAdverse eventsCohort 1Immune cell PD-L1 expressionInvestigator-assessed objective response ratePhase II open-label studyResponse rateIC PD-L1 expressionTumor cellsBaseline tumor samplesOpen-label studyPhase II studyProgression-free survivalResponse Evaluation CriteriaDuration of responseAtezolizumab monotherapyAdvanced NSCLCBrain metastasesMonotherapy studiesPrimary endpointSecondary endpointsII studyOverall survivalBrigatinib versus Crizotinib in ALK-Positive Non–Small-Cell Lung Cancer
Camidge DR, Kim HR, Ahn MJ, Yang JC, Han JY, Lee JS, Hochmair MJ, Li JY, Chang GC, Lee KH, Gridelli C, Delmonte A, Garcia Campelo R, Kim DW, Bearz A, Griesinger F, Morabito A, Felip E, Califano R, Ghosh S, Spira A, Gettinger SN, Tiseo M, Gupta N, Haney J, Kerstein D, Popat S. Brigatinib versus Crizotinib in ALK-Positive Non–Small-Cell Lung Cancer. New England Journal Of Medicine 2018, 379: 2027-2039. PMID: 30280657, DOI: 10.1056/nejmoa1810171.Peer-Reviewed Original ResearchConceptsProgression-free survivalALK-positive NSCLCAdvanced ALK-positive NSCLCObjective response rateFirst interim analysisALK inhibitorsLung cancerIntracranial responseInterim analysisNext-generation anaplastic lymphoma kinase (ALK) inhibitorResponse rateConfirmed objective response rateEnd pointSmall cell lung cancerBlinded independent central reviewAnaplastic lymphoma kinase inhibitorsEfficacy of brigatinibPrimary end pointSecondary end pointsPhase 3 trialALK-Positive NonCell lung cancerIndependent central reviewNew safety concernsCrizotinib groupSafety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study
Horn L, Gettinger SN, Gordon MS, Herbst RS, Gandhi L, Felip E, Sequist LV, Spigel DR, Antonia SJ, Balmanoukian A, Cassier PA, Liu B, Kowanetz M, O'Hear C, Fassò M, Grossman W, Sandler A, Soria JC. Safety and clinical activity of atezolizumab monotherapy in metastatic non-small-cell lung cancer: final results from a phase I study. European Journal Of Cancer 2018, 101: 201-209. PMID: 30077125, DOI: 10.1016/j.ejca.2018.06.031.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsBaseline PD-L1 expressionObjective response ratePD-L1 expressionPD-L1Immune cellsGrade treatment-related adverse eventsSurvival rateCell lung cancer cohortLong-term clinical benefitTumor-infiltrating immune cellsTumor cellsPhase IPrevious systemic therapySingle-agent atezolizumabCell lung cancerExploratory subgroup analysisLung cancer cohortAtezolizumab monotherapyAdverse eventsDurable responsesMedian durationSystemic therapyAnticancer immunityPD-1Exploratory Analysis of Brigatinib Activity in Patients With Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer and Brain Metastases in Two Clinical Trials.
Camidge DR, Kim DW, Tiseo M, Langer CJ, Ahn MJ, Shaw AT, Huber RM, Hochmair MJ, Lee DH, Bazhenova LA, Gold KA, Ou SI, West HL, Reichmann W, Haney J, Clackson T, Kerstein D, Gettinger SN. Exploratory Analysis of Brigatinib Activity in Patients With Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer and Brain Metastases in Two Clinical Trials. Journal Of Clinical Oncology 2018, 36: 2693-2701. PMID: 29768119, DOI: 10.1200/jco.2017.77.5841.Peer-Reviewed Original ResearchConceptsIntracranial progression-free survivalBaseline brain metastasesALK-positive NSCLCBrain metastasesIntracranial ORRArm ALung cancerAnaplastic Lymphoma Kinase-Positive NonMedian intracranial progression-free survivalPhase I/II trialNext-generation ALK inhibitorsSmall cell lung cancerMeasurable brain metastasesPrior brain radiotherapyResults Most patientsPrimary end pointProgression-free survivalCell lung cancerIndependent review committeeInitial disease progressionAnaplastic lymphoma kinase (ALK) geneIntracranial efficacyII trialPrior radiationBrain radiotherapyNivolumab 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
Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1–Selected Advanced Non–Small-Cell Lung Cancer (BIRCH)
Peters S, Gettinger S, Johnson ML, Jänne PA, Garassino MC, Christoph D, Toh CK, Rizvi NA, Chaft JE, Carcereny Costa E, Patel JD, Chow LQM, Koczywas M, Ho C, Früh M, van den Heuvel M, Rothenstein J, Reck M, Paz-Ares L, Shepherd FA, Kurata T, Li Z, Qiu J, Kowanetz M, Mocci S, Shankar G, Sandler A, Felip E. Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1–Selected Advanced Non–Small-Cell Lung Cancer (BIRCH). Journal Of Clinical Oncology 2017, 35: jco.2016.71.947. PMID: 28609226, PMCID: PMC5562171, DOI: 10.1200/jco.2016.71.9476.Peer-Reviewed Original ResearchConceptsMedian overall survivalOverall survivalImmune cellsPD-L1Tumor cellsLung cancerAdvanced non-small cell lung cancerNon-small cell lung cancerTumor-infiltrating immune cellsEnd pointEfficacy of atezolizumabEfficacy-evaluable patientsMethods Eligible patientsObjective response ratePrimary end pointSecondary end pointsLines of therapyPD-L1 expressionPD-L1 statusPhase II trialProgression-free survivalDeath ligand 1Cell lung cancerKRAS mutation statusAtezolizumab monotherapyBrigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase–Positive Non–Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial
Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, Huber RM, West HL, Groen HJM, Hochmair MJ, Leighl NB, Gettinger SN, Langer CJ, Paz-Ares Rodríguez LG, Smit EF, Kim ES, Reichmann W, Haluska FG, Kerstein D, Camidge DR. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase–Positive Non–Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial. Journal Of Clinical Oncology 2017, 35: jco.2016.71.590. PMID: 28475456, DOI: 10.1200/jco.2016.71.5904.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAnaplastic Lymphoma KinaseAntineoplastic AgentsBrain NeoplasmsCarcinoma, Non-Small-Cell LungCoughCrizotinibDiarrheaDisease ProgressionDisease-Free SurvivalFemaleHeadacheHumansLung NeoplasmsMaleMiddle AgedNauseaOrganophosphorus CompoundsProspective StudiesPyrazolesPyridinesPyrimidinesReceptor Protein-Tyrosine KinasesRetreatmentTreatment OutcomeYoung AdultConceptsObjective response rateProgression-free survivalBrain metastasesArm AAdverse eventsLung cancerInvestigator-assessed median progression-free survivalCommon treatment-emergent adverse eventsPositive non-small cell lung cancerNon-small cell lung cancerMedian progression-free survivalMulticenter phase II trialNext-generation ALK inhibitorsTreatment-emergent adverse eventsIntracranial objective response rateBaseline brain metastasesCrizotinib-treated patientsMeasurable brain metastasesPulmonary adverse eventsPrimary end pointPhase II trialCell lung cancerALK-positive NSCLCAnaplastic lymphoma kinase (ALK) geneAnaplastic lymphoma kinaseA 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
2016
PD-1 Axis Inhibitors in EGFR- and ALK-Driven Lung Cancer: Lost Cause?
Gettinger S, Politi K. PD-1 Axis Inhibitors in EGFR- and ALK-Driven Lung Cancer: Lost Cause? Clinical Cancer Research 2016, 22: 4539-4541. PMID: 27470969, PMCID: PMC5653962, DOI: 10.1158/1078-0432.ccr-16-1401.Peer-Reviewed Original ResearchNivolumab Monotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer
Gettinger S, Rizvi NA, Chow LQ, Borghaei H, Brahmer J, Ready N, Gerber DE, Shepherd FA, Antonia S, Goldman JW, Juergens RA, Laurie SA, Nathan FE, Shen Y, Harbison CT, Hellmann MD. Nivolumab Monotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2016, 34: 2980-2987. PMID: 27354485, PMCID: PMC5569692, DOI: 10.1200/jco.2016.66.9929.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsObjective response ratePD-ligand 1 (PD-L1) expressionAdverse eventsOverall survivalNivolumab monotherapyAdvanced NSCLCLung cancerGrade 3Death-1 immune checkpoint inhibitor antibodyAdvanced non-small cell lung cancerGrade treatment-related adverse eventsNon-small cell lung cancerImmune checkpoint inhibitor antibodyProgression-free survival ratesCheckpoint inhibitor antibodyExploratory end pointsFirst tumor assessmentFirst-line monotherapyOngoing complete responseTolerable safety profileMedian overall survivalGrade 3 rashOnly grade 3Cell lung cancerOncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells
Forloni M, Gupta R, Nagarajan A, Sun LS, Dong Y, Pirazzoli V, Toki M, Wurtz A, Melnick MA, Kobayashi S, Homer RJ, Rimm DL, Gettinger SJ, Politi K, Dogra SK, Wajapeyee N. Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells. Cell Reports 2016, 16: 457-471. PMID: 27346347, PMCID: PMC4945411, DOI: 10.1016/j.celrep.2016.05.087.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAntineoplastic AgentsBrain NeoplasmsCCAAT-Enhancer-Binding ProteinsCell Line, TumorCpG IslandsDNA MethylationDrug Screening Assays, AntitumorErbB ReceptorsGene Expression Regulation, NeoplasticGene SilencingGlioblastomaHumansLung NeoplasmsMAP Kinase Signaling SystemMixed Function OxygenasesMutationOncogenesProtein Kinase InhibitorsProto-Oncogene ProteinsTranscription, GeneticTumor Suppressor ProteinsUp-RegulationConceptsOncogenic epidermal growth factor receptorMethylation-mediated transcriptional silencingEpidermal growth factor receptorTumor suppressorTranscriptional silencingActive DNA demethylationCancer cellsFamily member 1TET1 knockdownDNA demethylaseDNA demethylationTranscription factorsGrowth factor receptorEctopic expressionCytoplasmic localizationGlioblastoma tumor growthLung cancer cellsTET1 expressionFunctional roleSuppressorFactor receptorMember 1TET1SilencingLung cancer samplesPembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohortPossible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases
Alomari AK, Cohen J, Vortmeyer AO, Chiang A, Gettinger S, Goldberg S, Kluger HM, Chiang VL. Possible Interaction of Anti–PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases. Cancer Immunology Research 2016, 4: 481-487. PMID: 26994250, DOI: 10.1158/2326-6066.cir-15-0238.Peer-Reviewed Original ResearchConceptsStereotactic radiosurgeryBrain metastasesInitiation of immunotherapyPD-1 mAbImmune-modulating therapyModalities of treatmentRadiologic progressionSurgical resectionSystemic therapyDeath-1Radiologic findingsMetastatic malignancyReactive astrocytosisPathologic examinationTreatment regimensHistopathologic examinationWall infiltrationT lymphocytesPatientsTumor progressionMonoclonal antibodiesBiologic interactionsRadiation-induced changesImmunotherapyMalignancyAssociation 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