2022
Cancer of the Lung
Morgensztern D, Boffa D, Chen A, Dhanasopon A, Goldberg S, Decker R, Devarakonda S, Ko J, Soto L, Waqar S, Wistuba I, Herbst R. Cancer of the Lung. 2022, 1-29. DOI: 10.1002/9781119000822.hfcm085.pub2.Peer-Reviewed Original ResearchBFAST but be smart: bTMB remains an exploratory biomarker in NSCLC
Kim SY, Herbst RS. BFAST but be smart: bTMB remains an exploratory biomarker in NSCLC. Nature Reviews Clinical Oncology 2022, 20: 3-4. PMID: 36271141, DOI: 10.1038/s41571-022-00698-y.Peer-Reviewed Original ResearchConceptsCell lung cancerTumor mutational burdenLung cancerMutational burdenBlood-based tumor mutational burdenAdvanced-stage solid tumorsFirst phase III trialHigh tumor mutational burdenImmune checkpoint inhibitorsPhase III trialsIII trialsPredictive biomarkersExploratory biomarkersCompanion biomarkersSolid tumorsBiomarkersCancerBurdenPembrolizumabNSCLCPatientsTumorsTrialsAddressing CPI resistance in NSCLC: targeting TAM receptors to modulate the tumor microenvironment and future prospects
Peters S, Paz-Ares L, Herbst RS, Reck M. Addressing CPI resistance in NSCLC: targeting TAM receptors to modulate the tumor microenvironment and future prospects. Journal For ImmunoTherapy Of Cancer 2022, 10: e004863. PMID: 35858709, PMCID: PMC9305809, DOI: 10.1136/jitc-2022-004863.Peer-Reviewed Original ResearchConceptsImmunosuppressive tumor microenvironmentCheckpoint inhibitorsTAM receptorsImmune responseTumor microenvironmentOverall survivalLung cancerStandard first-line therapyLong-term clinical responseCell death protein 1Immunostimulatory tumor microenvironmentImmune checkpoint inhibitorsInhibitor-based regimensFirst-line therapyAntitumor immune responseDeath protein 1Cell lung cancerPatients' overall survivalStrong biological rationaleNew treatment approachesLong-term survivalActivation of Tyro3Majority of casesCPI therapyAdvanced NSCLCProgrammed Death-Ligand 1 and Programmed Death-Ligand 2 mRNAs Measured Using Closed-System Quantitative Real-Time Polymerase Chain Reaction Are Associated With Outcome and High Negative Predictive Value in Immunotherapy-Treated NSCLC
Fernandez AI, Gavrielatou N, McCann L, Shafi S, Moutafi MK, Martinez-Morilla S, Vathiotis IA, Aung TN, Yaghoobi V, Bai Y, Chan YG, Weidler J, Herbst R, Bates M, Rimm DL. Programmed Death-Ligand 1 and Programmed Death-Ligand 2 mRNAs Measured Using Closed-System Quantitative Real-Time Polymerase Chain Reaction Are Associated With Outcome and High Negative Predictive Value in Immunotherapy-Treated NSCLC. Journal Of Thoracic Oncology 2022, 17: 1078-1085. PMID: 35764237, DOI: 10.1016/j.jtho.2022.06.007.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsHigh negative predictive valueLow stage patientsICI therapyPD-L1Negative predictive valueAdjuvant settingLong-term benefitsPredictive valueProgrammed Death Ligand 1PD-L1 mRNA levelsCurrent predictive biomarkersHigh PD-L1Death ligand 1Lung cancer managementPD-L1 mRNAUseful objective methodReal-time reverse transcription-polymerase chain reactionMRNA levelsStandard of careReverse transcription-polymerase chain reactionQuantitative real-time reverse transcription-polymerase chain reactionTranscription-polymerase chain reactionMRNA expression levelsAdvanced NSCLCRole of tumor infiltrating lymphocytes and spatial immune heterogeneity in sensitivity to PD-1 axis blockers in non-small cell lung cancer
de Rodas M, Nagineni V, Ravi A, Datar IJ, Mino-Kenudson M, Corredor G, Barrera C, Behlman L, Rimm DL, Herbst RS, Madabhushi A, Riess JW, Velcheti V, Hellmann MD, Gainor J, Schalper KA. Role of tumor infiltrating lymphocytes and spatial immune heterogeneity in sensitivity to PD-1 axis blockers in non-small cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e004440. PMID: 35649657, PMCID: PMC9161072, DOI: 10.1136/jitc-2021-004440.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsT-cell immunoglobulin mucin-3Cell lung cancerCytotoxic T cellsT cellsImmune heterogeneityLung cancerT cell exhaustion marker expressionPD-L1 positive patientsT cell exhaustion markersAdaptive antitumor immune responsesCell death protein 1Baseline tumor samplesExhaustion marker expressionIndependent NSCLC cohortsTumor immune heterogeneityT-cell densityAntitumor immune responseT cell infiltrationDeath protein 1Multi-institutional cohortActivation gene-3Helper T cellsRole of tumorFirst report of safety/tolerability and preliminary antitumor activity of CAN-2409 in inadequate responders to immune checkpoint inhibitors for stage III/IV NSCLC.
Aggarwal C, Haas A, Gordon S, Mehra R, Lee P, Bestvina C, Maldonado F, Velcheti V, Herbst R, Bell S, Gillmor R, Manzanera A, Matheny C, Aguilar-Cordova E, Aguilar L, Barone F, Tak P, Sterman D. First report of safety/tolerability and preliminary antitumor activity of CAN-2409 in inadequate responders to immune checkpoint inhibitors for stage III/IV NSCLC. Journal Of Clinical Oncology 2022, 40: 9037-9037. DOI: 10.1200/jco.2022.40.16_suppl.9037.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsStage III/IV NSCLCProgressive diseaseClinical responseAdvanced NSCLCEvaluable patientsCheckpoint inhibitorsInjected tumorsDisease-positive lymph nodesNon-injected lesionsSafety/tolerabilitySubset of patientsT cell infiltrationPreliminary antitumor activityPreliminary clinical dataTumor cell lysisMedicine clinical trialsRational combination approachesIntra-tumoral deliveryStable diseaseData cutoffDisease stabilizationImmunologic biomarkersOral valacyclovirMedian durationA phase II study of talazoparib plus avelumab in patients with stage IV or recurrent nonsquamous non–small cell lung cancer bearing pathogenic STK11 genomic alterations (SWOG S1900C, LUNG-MAP sub-study, NCT04173507).
Skoulidis F, Redman M, Suga J, Al Baghdadi T, Villano J, Goldberg S, Villaruz L, Minichiello K, Gandara D, Herbst R, Kelly K. A phase II study of talazoparib plus avelumab in patients with stage IV or recurrent nonsquamous non–small cell lung cancer bearing pathogenic STK11 genomic alterations (SWOG S1900C, LUNG-MAP sub-study, NCT04173507). Journal Of Clinical Oncology 2022, 40: 9060-9060. DOI: 10.1200/jco.2022.40.16_suppl.9060.Peer-Reviewed Original ResearchObjective response ratePhase II studyCheckpoint inhibitorsII studyStage IVPrior linesGenomic alterationsSingle-arm phase II studyArm phase II studyBest objective response rateMedian progression-free survivalPARP inhibitorsAdequate organ functionCo-primary objectivesDurable disease stabilizationMost grade 3PD-L1 TPSDisease control rateImmune checkpoint inhibitorsMedian overall survivalNon-squamous NSCLCStage IV diseaseProgression-free survivalBest objective responseOptimal therapeutic approachSociety for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma
Govindan R, Aggarwal C, Antonia SJ, Davies M, Dubinett SM, Ferris A, Forde PM, Garon EB, Goldberg SB, Hassan R, Hellmann MD, Hirsch FR, Johnson ML, Malik S, Morgensztern D, Neal JW, Patel JD, Rimm DL, Sagorsky S, Schwartz LH, Sepesi B, Herbst RS. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma. Journal For ImmunoTherapy Of Cancer 2022, 10: e003956. PMID: 35640927, PMCID: PMC9157337, DOI: 10.1136/jitc-2021-003956.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSmall cell lung cancerClinical practice guidelinesLung cancerQuality of lifePractice guidelinesTreatment of NSCLCImmune-related adverse eventsCancer clinical practice guidelinesLung cancer careImmune checkpoint inhibitorsUse of immunotherapyFirst-line therapySubset of patientsCell lung cancerCancer care providersImmunotherapy of cancerConsensus-based recommendationsAdjuvant settingAdvanced diseaseCheckpoint inhibitorsAdverse eventsDurable responsesThoracic malignanciesAutoimmune disordersDiscovery of Biomarkers of Resistance to Immune Checkpoint Blockade in NSCLC Using High-Plex Digital Spatial Profiling
Moutafi M, Martinez-Morilla S, Divakar P, Vathiotis I, Gavrielatou N, Aung TN, Yaghoobi V, Fernandez AI, Zugazagoitia J, Herbst R, Schalper KA, Rimm DL. Discovery of Biomarkers of Resistance to Immune Checkpoint Blockade in NSCLC Using High-Plex Digital Spatial Profiling. Journal Of Thoracic Oncology 2022, 17: 991-1001. PMID: 35490853, PMCID: PMC9356986, DOI: 10.1016/j.jtho.2022.04.009.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsICI resistanceDigital spatial profilingICI therapyOverall survivalPretreatment samplesQuantitative immunofluorescenceImmune checkpoint blockadeRole of neutrophilsShorter overall survivalCandidate biomarker proteinsCandidate protein biomarkersCohort validationOperable NSCLCUntreated NSCLCCheckpoint inhibitorsCheckpoint blockadeCD66b expressionAdditional patientsClinical efficacyPoor outcomeDiscovery of biomarkersUnivariate analysisNSCLCPatients
2021
Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC
Grant MJ, Herbst RS, Goldberg SB. Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC. Nature Reviews Clinical Oncology 2021, 18: 625-644. PMID: 34168333, DOI: 10.1038/s41571-021-00520-1.Peer-Reviewed Original ResearchConceptsSubset of patientsTreatment landscapeRegimen selectionTumor cell PD-L1 expressionChemotherapy-immunotherapy combinationsImmune checkpoint inhibitorsTreatment-naive patientsFirst-line therapyPD-L1 expressionCurrent treatment landscapeCell lung cancerAbsence of headCurrent treatment paradigmsPivotal clinical trialsLong-term efficacyNovel therapeutic strategiesImmunotherapy regimenMetastatic NSCLCImmunotherapeutic strategiesClinicopathological factorsPD-1PD-L1Durable efficacyHistological subtypesLung cancer
2020
PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice
Eguren-Santamaria I, Sanmamed MF, Goldberg SB, Kluger HM, Idoate MA, Lu B, Corral J, Schalper KA, Herbst RS, Gil-Bazo I. PD-1/PD-L1 Blockers in NSCLC Brain Metastases: Challenging Paradigms and Clinical Practice. Clinical Cancer Research 2020, 26: 4186-4197. PMID: 32354698, DOI: 10.1158/1078-0432.ccr-20-0798.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsAnti-PD-1/PD-L1 antibodiesAdvanced non-small cell lung cancerNSCLC brain metastasesBrain metastasesPD-L1 antibodiesAnti-PD-1/PD-L1 agentsPD-1/PD-L1 blockersActive central nervous system (CNS) involvementHigh PD-L1 expressionAnti-PD-1/PD-L1 drugsCentral nervous system involvementPivotal phase III trialsActive brain metastasesCNS response ratesPD-L1 agentsPD-L1 blockersSystemic therapy combinationsNervous system involvementPD-L1 expressionPhase III trialsSubset of patientsCell lung cancerPD-L1 drugsImmune 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
SY6-1 Cancer immunotherapy; A paradigm shift in the first-line treatment of lung cancer
Herbst R. SY6-1 Cancer immunotherapy; A paradigm shift in the first-line treatment of lung cancer. Annals Of Oncology 2019, 30: vi32. DOI: 10.1093/annonc/mdz325.Peer-Reviewed Original ResearchLung cancerImmune checkpoint inhibitorsFirst-line treatmentMinority of patientsTumor mutational burdenPresence of tumorEfficient trial designMarker of resistanceCheckpoint inhibitorsTreatment of cancerCancer deathCancer immunotherapyPredictive markerSmoking ratesMutational burdenNew therapiesTrial designImmune systemCancerTherapyImmunotherapyChemotherapyPatientsTreatmentMarkersImmunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes
Doroshow DB, Sanmamed MF, Hastings K, Politi K, Rimm DL, Chen L, Melero I, Schalper KA, Herbst RS. Immunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes. Clinical Cancer Research 2019, 25: 4592-4602. PMID: 30824587, PMCID: PMC6679805, DOI: 10.1158/1078-0432.ccr-18-1538.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNon-small cell lung cancerImmune checkpoint inhibitorsCell lung cancerPD-L1Lung cancerNonsquamous non-small cell lung cancerOngoing translational workPD-1 axisFirst-line therapyPD-L1 expressionProportion of patientsTumor mutational burdenAdvanced diseaseOverall survivalTumor inflammationMutational burdenPatientsNovel markerChemotherapyTherapyIndicative biomarkersCancerTranslational workBiomarkersSurvivalBiomarker-directed precision oncology of pembrolizumab-based combination therapy for non-small cell lung cancer: Phase II KEYNOTE-495/KeyImPaCT study.
Gutierrez M, Hellmann M, Gubens M, Aggarwal C, Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Basso A, Ma H, Fong L, Snyder A, Yuan J, Herbst R. Biomarker-directed precision oncology of pembrolizumab-based combination therapy for non-small cell lung cancer: Phase II KEYNOTE-495/KeyImPaCT study. Journal Of Clinical Oncology 2019, 37: tps9117-tps9117. DOI: 10.1200/jco.2019.37.15_suppl.tps9117.Peer-Reviewed Original ResearchCombination therapyRECIST v1.1Advanced NSCLCGene expression profilesInvestigator-assessed objective response rateNon-small cell lung cancerEnd pointT-cell-inflamed gene expression profileECOG PS 0Immune checkpoint inhibitorsObjective response ratePrimary end pointSecondary end pointsProgression-free survivalROS1 gene rearrangementCell lung cancerAbsence of EGFRInterim efficacy analysisDifferent combination therapiesCombination immunotherapyLenvatinib armLenvatinib monotherapyMeasurable diseaseCheckpoint inhibitorsPembrolizumab monotherapyEGFR 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 casesImmune 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
The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC)
Brahmer JR, Govindan R, Anders RA, Antonia SJ, Sagorsky S, Davies MJ, Dubinett SM, Ferris A, Gandhi L, Garon EB, Hellmann MD, Hirsch FR, Malik S, Neal JW, Papadimitrakopoulou VA, Rimm DL, Schwartz LH, Sepesi B, Yeap BY, Rizvi NA, Herbst RS. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC). Journal For ImmunoTherapy Of Cancer 2018, 6: 75. PMID: 30012210, PMCID: PMC6048854, DOI: 10.1186/s40425-018-0382-2.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsCell lung cancerCheckpoint inhibitorsLung cancerDurable responsesConsensus statementStage III non-small cell lung cancerAdvanced non-small cell lung cancerCancer consensus statementSequencing of therapySecond-line settingAppropriate patient selectionOnly treatment optionAdverse event managementCancer-related mortalityImmunotherapy of cancerEvidence-based recommendationsNew treatment approachesStrength of evidenceAdvanced diseasePatient selectionTargetable mutationsTreatment optionsCancer immunotherapyEarly 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 time
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