2020
Immune 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
2019
Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer
Zugazagoitia J, Liu Y, Toki M, McGuire J, Ahmed FS, Henick BS, Gupta R, Gettinger S, Herbst R, Schalper KA, Rimm DL. Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: 2084-2096. PMID: 31605795, PMCID: PMC6951804, DOI: 10.1016/j.jtho.2019.09.014.Peer-Reviewed Original ResearchConceptsPD-L1CMTM6 expressionPathway blockadeAdvanced stage non-small cell lung cancerNon-small cell lung cancerPD-1 pathway blockadeTumor cellsAbsence of immunotherapyMultiplexed quantitative immunofluorescencePD-L1 coexpressionStromal immune cellsPD-L1 expressionT cell infiltrationLonger overall survivalCell lung cancerIndependent retrospective cohortsKRAS mutational statusExpression of CMTM6MARVEL transmembrane domainNSCLC cohortOverall survivalRetrospective cohortAxis blockadeClinical featuresImmunotherapy outcomes
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 survivalDifferential 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 stromaSafety 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-1
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
2015
3017 NSCLC with high PD-L1 expression on tumor cells or tumorinfiltrating immune cells represents distinct cancer subtypes
Schmid P, Kowanetz M, Koeppen H, Zou W, Wistuba I, Kockx M, Kadel E, Chaft J, Rizvi N, Hirsch F, Smith D, Miley N, Leveque V, Shames D, Sandler A, Mellman I, Chen D, Hegde P, Gettinger S. 3017 NSCLC with high PD-L1 expression on tumor cells or tumorinfiltrating immune cells represents distinct cancer subtypes. European Journal Of Cancer 2015, 51: s602. DOI: 10.1016/s0959-8049(16)31661-6.Peer-Reviewed Original Research
2014
1322P Biomarkers Associated with Clinical Activity of Pd-L1 Blockade in Non-Small Cell Lung Cancer (Nsclc) Patients (Pts) in a Phase I Study of Mpdl3280A
Soria J, Gettinger S, Gordon M, Heist R, Horn L, Spigel D, Kowanetz M, Mokatrin A, Xiao Y, Sandler A, Felip E. 1322P Biomarkers Associated with Clinical Activity of Pd-L1 Blockade in Non-Small Cell Lung Cancer (Nsclc) Patients (Pts) in a Phase I Study of Mpdl3280A. Annals Of Oncology 2014, 25: iv465. DOI: 10.1093/annonc/mdu349.101.Peer-Reviewed Original ResearchPD-L1 expressionPD-L1 blockadeIHC 2PD-L1Immune cellsNSCLC ptsB7-H4B7-H3PD-L2Tumor cellsIHC 0Clinical activityNon-small cell lung cancer patientsTumor-infiltrating immune cellsCell lung cancer patientsEmployees of GenentechReceptor PD-1Tumor immune microenvironmentLung cancer patientsPD-L1 IHCPD-L1 bindingRoche/GenentechImmune-related genesBristol-Myers SquibbPFS rates