2020
Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer
Hellmann MD, Gettinger S, Chow LQM, Gordon M, Awad MM, Cha E, Gong X, Zhou G, Walker C, Leopold L, Heist RS. Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer. International Journal Of Cancer 2020, 147: 1963-1969. PMID: 32141617, PMCID: PMC7496129, DOI: 10.1002/ijc.32951.Peer-Reviewed Original ResearchConceptsNonsmall cell lung cancerTreatment-related adverse eventsDose-limiting toxicityCell lung cancerAdverse eventsLung cancerStage IIIB/IV nonsmall cell lung cancerFatal treatment-related adverse eventsAdvanced nonsmall cell lung cancerCell death ligand 1Grade 3 dehydrationGrade 3 hyponatremiaGrade 3/4 eventsPhase 1 studyPlatinum-based chemotherapyDeath ligand 1Dose of treatmentAutoimmune encephalitisEligible patientsIntravenous atezolizumabStable diseasePrimary endpointPartial responsePrior linesIDO expressionImmune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy
Liu Y, Zugazagoitia J, Ahmed FS, Henick BS, Gettinger S, Herbst RS, Schalper KA, Rimm DL. Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy. Clinical Cancer Research 2020, 26: 970-977. PMID: 31615933, PMCID: PMC7024671, DOI: 10.1158/1078-0432.ccr-19-1040.Peer-Reviewed Original ResearchConceptsPD-L1 expressionHigh PD-L1 expressionPD-L1 levelsPD-L1Immune cellsTumor cellsT cellsHigh PD-L1 levelsPredominant immune cell typeNon-small cell lung cancer (NSCLC) casesDifferent immune cell subsetsCell lung cancer casesElevated PD-L1High PD-L1Better overall survivalDeath ligand 1Natural killer cellsImmune cell subsetsMultiple immune cellsCytotoxic T cellsLung cancer casesImmune cell typesCD68 levelsCell typesBlockade therapy
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 monotherapy
2016
Clinical and Histologic Features of Lichenoid Mucocutaneous Eruptions Due to Anti–Programmed Cell Death 1 and Anti–Programmed Cell Death Ligand 1 Immunotherapy
Shi VJ, Rodic N, Gettinger S, Leventhal JS, Neckman JP, Girardi M, Bosenberg M, Choi JN. Clinical and Histologic Features of Lichenoid Mucocutaneous Eruptions Due to Anti–Programmed Cell Death 1 and Anti–Programmed Cell Death Ligand 1 Immunotherapy. JAMA Dermatology 2016, 152: 1128-1136. PMID: 27411054, PMCID: PMC6108080, DOI: 10.1001/jamadermatol.2016.2226.Peer-Reviewed Original ResearchConceptsAnti-PD-1/PD-L1 therapyCutaneous adverse effectsPD-L1 therapyCell death 1Concurrent medicationsDeath-1Adverse effectsClinical morphologyAnti-PD-1/PD-L1 treatmentAnti-programmed cell death ligand-1 (PD-L1) immunotherapiesAnti-programmed cell death 1Non-small cell lung cancerDeath ligand 1 (PD-L1) immunotherapyPD-L1 antibody therapyCell death ligand 1Yale-New Haven HospitalMucocutaneous adverse effectsPD-L1 treatmentTreatment of rashTertiary care hospitalDeath ligand 1Lichenoid drug eruptionCell lung cancerSkin biopsy specimensRecent US Food
2015
Immune Checkpoint Modulation for Non–Small Cell Lung Cancer
Soria JC, Marabelle A, Brahmer JR, Gettinger S. Immune Checkpoint Modulation for Non–Small Cell Lung Cancer. Clinical Cancer Research 2015, 21: 2256-2262. PMID: 25979932, DOI: 10.1158/1078-0432.ccr-14-2959.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerImmune checkpointsL1 antibodyLung cancerClinical trialsT cellsImmune-related progression-free survivalCytotoxic T-lymphocyte-associated protein 4Response rateT-lymphocyte-associated protein 4Tumor PD-L1 expressionRandomized phase II trialImmune checkpoint modulationObjective response ratePD-L1 expressionPhase II trialProgression-free survivalDeath ligand 1Immunosuppressive T cellsAdditional clinical trialsLung cancer patientsLow toxicity profileNSCLC histology
2014
B7-H1/PD-1 Blockade Therapy in Non–Small Cell Lung Cancer
Gettinger S, Herbst RS. B7-H1/PD-1 Blockade Therapy in Non–Small Cell Lung Cancer. The Cancer Journal 2014, 20: 281-289. PMID: 25098289, DOI: 10.1097/ppo.0000000000000063.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerPhase III trialsCell lung cancerIII trialsPD-1Lung cancerClinical trialsPD-1/PD-L1 inhibitorsB7-H1/PDTumor PD-L1 expressionSevere autoimmune toxicityChemotherapy-naive patientsPD-L1 expressionPotential of immunotherapyPD-L1 inhibitorsDeath ligand 1Future clinical trialsNumber of antibodiesAutoimmune toxicityExpansion cohortBlockade therapyDurable responsesNSCLC patientsStandard therapy
2013
Programmed death ligand-1 expression in non-small cell lung cancer
Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M, Herbst RS, Gettinger SN, Chen L, Rimm DL. Programmed death ligand-1 expression in non-small cell lung cancer. Laboratory Investigation 2013, 94: 107-116. PMID: 24217091, PMCID: PMC6125250, DOI: 10.1038/labinvest.2013.130.Peer-Reviewed Original ResearchMeSH KeywordsAgedB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Line, TumorChi-Square DistributionCohort StudiesConnecticutFemaleGreeceHumansImmunohistochemistryLung NeoplasmsLymphocytes, Tumor-InfiltratingMalePrognosisReproducibility of ResultsRNA, MessengerSurvival AnalysisTissue Array AnalysisConceptsNon-small cell lung cancerPD-L1 expressionCell lung cancerPD-L1Tissue microarrayBetter outcomesNSCLC casesLung cancerDeath ligand 1 (PD-L1) expressionCell death ligand 1PD-L1 protein expressionEarly phase clinical trialsLigand 1 expressionTumor-infiltrating lymphocytesDeath ligand 1Significant better outcomePD-L1 mRNAPD-L1 proteinPhase clinical trialsNormal human placentaPrediction of responseQuantitative fluorescence approachesFrequency of expressionPD-1Prognostic valueClinical significance of programmed death ligand-1 expression in non-small cell lung cancer (NSCLC).
Velcheti V, Schalper K, Carvajal D, Chen L, Sznol M, Gettinger S, Herbst R, Rimm D. Clinical significance of programmed death ligand-1 expression in non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2013, 31: 11075-11075. DOI: 10.1200/jco.2013.31.15_suppl.11075.Peer-Reviewed Original ResearchNon-small cell lung cancerTumor-infiltrating lymphocytesPresence of TILsGreek cohortBetter outcomesPDL1 expressionNSCLC casesProtein positivityAnti-PD-1 therapyDeath ligand 1 (PD-L1) expressionCell death ligand 1Quantitative immunofluorescenceComparable prognostic informationIndependent NSCLC cohortsPDL1 protein expressionLigand 1 expressionLonger overall survivalPDL1 mRNADeath ligand 1Cell lung cancerMRNA levelsAQUA methodNormal human placentaNSCLC cohortOverall survival