2018
Differential 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
2014
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014, 515: 563-567. PMID: 25428504, PMCID: PMC4836193, DOI: 10.1038/nature14011.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkersChemokine CX3CL1Clinical ProtocolsCTLA-4 AntigenDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasmsTreatment OutcomeYoung Adult1322P 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