2024
Updated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC).
Aggarwal C, Martinez-Marti A, Majem M, Barlesi F, Carcereny E, Chu Q, Monnet I, Sanchez A, Dakhil S, Camidge D, Pillet M, Brown M, Dowson A, Cooper Z, Kumar R, Herbst R. Updated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC). Journal Of Clinical Oncology 2024, 42: 8046-8046. DOI: 10.1200/jco.2024.42.16_suppl.8046.Peer-Reviewed Original ResearchUnresectable non-small cell lung cancerStage III unresectable non-small cell lung cancerProgression free survivalImmune-mediated AEConcurrent chemoradiotherapyPhase 2 studyNon-small cell lung cancerProlonged progression free survivalECOG PS 0Suppress antitumor immunityMedian follow-upCell lung cancerExpression of CD73Anti-CD73Anti-NKG2AImmunotherapy combinationsAntitumor immunityConsolidation therapyPD-L1Free survivalImmune checkpointsPS 0Open-labelProgressive diseaseDiscontinued treatment
2022
Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer.
Shafi S, Aung T, Xirou V, Gavrielatou N, Vathiotis I, Fernandez A, Moutafi M, Yaghoobi V, Herbst R, Liu L, Langermann S, Rimm D. Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer. Laboratory Investigation 2022, 102: 1143-1149. PMID: 36775354, DOI: 10.1038/s41374-022-00796-6.Peer-Reviewed Original ResearchConceptsSiglec-15 expressionNon-small cell lung cancerNeck squamous cell carcinomaProgression-free survivalSquamous cell carcinomaCancer typesOverall survivalCell carcinomaBladder cancerImmune cellsSiglec-15PD-1/PD-L1 blockadePotential future clinical trialsQuantitative immunofluorescencePD-L1 blockadeStromal immune cellsImmune checkpoint blockadeCell lung cancerFuture clinical trialsNew potential targetsCheckpoint blockadePD-L1Lung cancerClinical trialsIntra-tumoral heterogeneitySpatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small-cell lung cancer
Moutafi MK, Molero M, Morilla S, Baena J, Vathiotis IA, Gavrielatou N, Castro-Labrador L, de Garibay GR, Adradas V, Orive D, Valencia K, Calvo A, Montuenga LM, Aix S, Schalper KA, Herbst RS, Paz-Ares L, Rimm DL, Zugazagoitia J. Spatially resolved proteomic profiling identifies tumor cell CD44 as a biomarker associated with sensitivity to PD-1 axis blockade in advanced non-small-cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e004757. PMID: 36002182, PMCID: PMC9413286, DOI: 10.1136/jitc-2022-004757.Peer-Reviewed Original ResearchConceptsProgression-free survivalPD-1 axis blockadePD-1 axis inhibitorsTumor proportion scoreCell lung cancerAxis blockadeQuantitative immunofluorescenceAxis inhibitionLung cancerCD44 levelsCD44 expressionTumor compartmentsLonger progression-free survivalAbsence of immunotherapyYale Cancer CenterWhole tissue sectionsQIF scoresExternal independent validationMost patientsOverall survivalTim-3Immune compartmentImmunotherapy strategiesPD-L1Untreated cohortProgrammed 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 NSCLCQuantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer
Shafi S, Aung TN, Xirou V, Gavrielatou N, Vathiotis IA, Fernandez A, Moutafi M, Yaghoobi V, Herbst RS, Liu LN, Langermann S, Rimm DL. Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer. Laboratory Investigation 2022, 102: 1143-1149. PMID: 35581307, PMCID: PMC10211373, DOI: 10.1038/s41374-022-00796-6.Peer-Reviewed Original ResearchConceptsSiglec-15 expressionNon-small cell lung cancerNeck squamous cell carcinomaProgression-free survivalSquamous cell carcinomaCancer typesOverall survivalCell carcinomaBladder cancerImmune cellsSiglec-15PD-1/PD-L1 blockadePotential future clinical trialsQuantitative immunofluorescencePD-L1 blockadeStromal immune cellsImmune checkpoint blockadeCell lung cancerFuture clinical trialsNew potential targetsCheckpoint blockadePD-L1Lung cancerClinical trialsIntra-tumoral heterogeneityDevelopment of an immunohistochemical assay for Siglec-15
Shafi S, Aung TN, Robbins C, Zugazagoitia J, Vathiotis I, Gavrielatou N, Yaghoobi V, Fernandez A, Niu S, Liu LN, Cusumano ZT, Leelatian N, Cole K, Wang H, Homer R, Herbst RS, Langermann S, Rimm DL. Development of an immunohistochemical assay for Siglec-15. Laboratory Investigation 2022, 102: 771-778. PMID: 35459795, PMCID: PMC9253057, DOI: 10.1038/s41374-022-00785-9.Peer-Reviewed Original ResearchConceptsSiglec-15IHC assaysPD-L1PD-1/PD-L1 inhibitionPD-L1 blockadePD-L1 inhibitionHigh expressionFuture clinical trialsImmunoglobulin-type lectinsSiglec-15 expressionCompanion diagnostic assayPromising new targetTumor histologyImmunotherapeutic targetLung cancerImmune cellsClinical trialsNovel recombinant antibodiesCancer histologyImmunohistochemical assaysMyeloid cellsTumor typesScoring systemNew targetsHigh concordance
2021
61P IMpower110: Exploratory analyses of the impact of first-line (1L) atezolizumab on the efficacy of next-line of therapy in PD-L1–selected NSCLC
Patel S, Reuss J, Scilla K, Giaccone G, Spigel D, Ngiam C, Zhu Q, Bara I, Ding B, Herbst R. 61P IMpower110: Exploratory analyses of the impact of first-line (1L) atezolizumab on the efficacy of next-line of therapy in PD-L1–selected NSCLC. Annals Of Oncology 2021, 32: s1398-s1399. DOI: 10.1016/j.annonc.2021.10.079.Peer-Reviewed Original Research364 KRAS mutations in patients with nonsquamous non–small-cell lung cancer: prevalence and relationship with PD-L1 expression, tumor mutation burden and smoking status
Garassino M, Rodriguez-Abreu D, Gadgeel S, Kowalski D, Kasahara K, Felip E, Wu Y, de Castro G, Cho B, Turna H, Horinouchi H, Reck M, Hui R, Garon E, Boyer M, Mok T, Lopes G, Kobie J, Li Y, Ayers M, Cristescu R, Zhao B, Pietanza M, Herbst R. 364 KRAS mutations in patients with nonsquamous non–small-cell lung cancer: prevalence and relationship with PD-L1 expression, tumor mutation burden and smoking status. Journal For ImmunoTherapy Of Cancer 2021, 9: a391-a391. DOI: 10.1136/jitc-2021-sitc2021.364.Peer-Reviewed Original ResearchPD-L1 TPSKRAS G12C mutationPD-L1 expressionPlatinum-based chemotherapyTumor PD-L1 expressionEGFR/ALK alterationsFirst-line therapyNon-squamous NSCLCNonsquamous NSCLCTumor mutation burdenPembrolizumab monotherapyKRAS mutational statusKEYNOTE-042KEYNOTE-189KRAS mutationsFormer smokersG12C mutationPatient characteristicsALK alterationsPD-L1Smoking statusMutation burdenKRAS G12CHigh tumor PD-L1 expressionMutational statusOutcomes With Pembrolizumab Monotherapy in Patients With Programmed Death-Ligand 1–Positive NSCLC With Brain Metastases: Pooled Analysis of KEYNOTE-001, 010, 024, and 042
Mansfield AS, Herbst RS, de Castro G, Hui R, Peled N, Kim DW, Novello S, Satouchi M, Wu YL, Garon EB, Reck M, Robinson AG, Samkari A, Piperdi B, Ebiana V, Lin J, Mok TSK. Outcomes With Pembrolizumab Monotherapy in Patients With Programmed Death-Ligand 1–Positive NSCLC With Brain Metastases: Pooled Analysis of KEYNOTE-001, 010, 024, and 042. JTO Clinical And Research Reports 2021, 2: 100205. PMID: 34590048, PMCID: PMC8474394, DOI: 10.1016/j.jtocrr.2021.100205.Peer-Reviewed Original ResearchBaseline brain metastasesPD-L1 TPSStable brain metastasesBrain metastasesKEYNOTE-001Metastatic NSCLCPembrolizumab monotherapyAdverse eventsPD-L1Treatment-related adverse eventsBrain metastasis statusEfficacy of pembrolizumabObjective response rateProgression-free survivalCell lung cancerDuration of responseKEYNOTE-010KEYNOTE-024KEYNOTE-042Data cutoffOverall survivalLung cancerMetastasis statusPresence of baselineChemotherapySelecting 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 cancerFP13.01 5-Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel in Previously Treated, PD-L1–Positive Advanced NSCLC
Herbst R, Garon E, Kim D, Cho B, Gervais R, Perez-Gracia J, Han J, Majem M, Forster M, Monnet I, Novello S, Gubens M, Boyer M, Su W, Samkari A, Jensen E, Piperdi B, Baas P. FP13.01 5-Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel in Previously Treated, PD-L1–Positive Advanced NSCLC. Journal Of Thoracic Oncology 2021, 16: s223-s224. DOI: 10.1016/j.jtho.2021.01.140.Peer-Reviewed Original ResearchFP13.03 IMpower110: Updated OS Analysis of Atezolizumab vs Platinum-Based Chemotherapy as First-Line Treatment in PD-L1–Selected NSCLC
Herbst R, De Marinis F, Giaccone G, Vergnenegre A, Barrios C, Morise M, Felip E, Oprean C, Kim Y, Andric Z, Mocci S, Enquist I, Komatsubara K, Mccleland M, Deng Y, Kuriki H, Villalobos M, Phan S, Spigel D, Jassem J. FP13.03 IMpower110: Updated OS Analysis of Atezolizumab vs Platinum-Based Chemotherapy as First-Line Treatment in PD-L1–Selected NSCLC. Journal Of Thoracic Oncology 2021, 16: s224-s225. DOI: 10.1016/j.jtho.2021.01.142.Peer-Reviewed Original Research
2020
Ramucirumab in Combination with Pembrolizumab in Treatment-Naïve Advanced Gastric or GEJ Adenocarcinoma: Safety and Antitumor Activity from the Phase 1a/b JVDF Trial
Chau I, Penel N, Soriano AO, Arkenau HT, Cultrera J, Santana-Davila R, Calvo E, Le Tourneau C, Zender L, Bendell JC, Mi G, Gao L, McNeely SC, Oliveira JM, Ferry D, Herbst RS, Fuchs CS. Ramucirumab in Combination with Pembrolizumab in Treatment-Naïve Advanced Gastric or GEJ Adenocarcinoma: Safety and Antitumor Activity from the Phase 1a/b JVDF Trial. Cancers 2020, 12: 2985. PMID: 33076423, PMCID: PMC7602637, DOI: 10.3390/cancers12102985.Peer-Reviewed Original ResearchObjective response rateProgression-free survivalOverall survivalPD-L1GEJ cancerGrade 3 treatment-related adverse eventsTreatment-related adverse eventsAlanine/aspartate aminotransferaseDurable clinical activityFirst-line patientsPrior systemic chemotherapyAntitumor activityDuration of responseSpectrum of patientsStudy design limitationsCheckpoint inhibitorsMetastatic settingPrimary endpointSecondary endpointsSystemic chemotherapyTreatment-naïveAdvanced gastricAdverse eventsAdvanced cancerPositive tumorsAtezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC
Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, Özgüroğlu M, Zou W, Sandler A, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, McCleland M, Mocci S, Jassem J, Spigel DR. Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC. New England Journal Of Medicine 2020, 383: 1328-1339. PMID: 32997907, DOI: 10.1056/nejmoa1917346.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenCarboplatinCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCisplatinDeoxycytidineFemaleGemcitabineHumansLung NeoplasmsMaleMiddle AgedMutationSurvival AnalysisConceptsPD-L1 expressionBlood-based tumor mutational burdenProgression-free survivalPlatinum-based chemotherapyTumor mutational burdenOverall survivalWild-type tumorsAtezolizumab groupChemotherapy groupAdverse eventsPD-L1Mutational burdenHigh PD-L1 expressionPD-L1 expression statusTumor-infiltrating immune cellsMedian overall survivalFirst-line treatmentPD-L1 assaysPhase 3 trialLonger overall survivalSubgroup of patientsCell lung cancerAtezolizumab treatmentSquamous NSCLCTreat populationPatient-reported outcomes (PROs) in the randomized, phase III IMpower110 study of atezolizumab (atezo) vs chemotherapy in 1L metastatic NSCLC.
de Marinis F, Giaccone G, Herbst R, Oprean C, Szczesna A, Boukovinas I, Bonomi L, Kim Y, Summers Y, Kurata T, Komatsubara K, Chen M, Deng Y, Kuriki H, Mocci S, Phan S, Jassem J, Spigel D. Patient-reported outcomes (PROs) in the randomized, phase III IMpower110 study of atezolizumab (atezo) vs chemotherapy in 1L metastatic NSCLC. Journal Of Clinical Oncology 2020, 38: 9594-9594. DOI: 10.1200/jco.2020.38.15_suppl.9594.Peer-Reviewed Original ResearchPatient-reported outcomesGlobal health statusLung cancer-related symptomsLung cancer symptomsCancer-related symptomsChest painWk 48Metastatic NSCLCSymptom burdenPhysical functionCancer symptomsLife Questionnaire Core 30Carboplatin AUC 6Overall clinical benefitStart of treatmentCompletion ratesAUC 5AUC 6Gemcitabine 1250Meaningful worseningNausea/OS benefitQLQ-LC13Primary endpointPD-L1IMpower110: Clinical safety in a phase III study of atezolizumab (atezo) monotherapy (mono) vs platinum-based chemotherapy (chemo) in first-line non-small cell lung cancer (NSCLC).
Jassem J, Herbst R, de Marinis F, Cadranel J, Csőszi T, Isla D, Chen G, Syrigos K, Cortinovis D, Hida T, Mocci S, Phan S, Enquist I, Patel H, Villalobos M, Wen X, Deng Y, Kuriki H, Spigel D, Giaccone G. IMpower110: Clinical safety in a phase III study of atezolizumab (atezo) monotherapy (mono) vs platinum-based chemotherapy (chemo) in first-line non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2020, 38: e21623-e21623. DOI: 10.1200/jco.2020.38.15_suppl.e21623.Peer-Reviewed Original ResearchNon-small cell lung cancerPD-L1 expressionSafety profileFirst‐line non‐small cell lung cancerCarboplatin AUC 6ECOG PS 0NCI CTCAE v4.0Chemo-naive patientsNew safety signalsPhase III studyPlatinum-based chemotherapyFavorable safety profileCell lung cancerAtezolizumab monotherapyAUC 5AUC 6Gemcitabine 1250Endocrine therapySystemic glucocorticoidsCTCAE v4.0Data cutoffIII studyPS 0PD-L1GEM 1000O81 IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (ATEZO) monotherapy vs platinum-based chemotherapy (CHEMO) as first-line (1L) treatment in PD-L1–selected NSCLC
Herbst R, De Marinis F, Giaccone G, Reinmuth N, Vergnenegre A, Barrios C, Morise M, Font E, Andric Z, Geater S, Ozguroglu M, Mocci S, McCleland M, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, Jassem J, Spigel D. O81 IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (ATEZO) monotherapy vs platinum-based chemotherapy (CHEMO) as first-line (1L) treatment in PD-L1–selected NSCLC. Journal For ImmunoTherapy Of Cancer 2020, 8: a1. DOI: 10.1136/lba2019.1.Peer-Reviewed Original ResearchTreatment-related AEsPD-L1 expressionPrimary endpointArm APD-L1Interim overall survival analysisTumor PD-L1 statusPD-L1/PDCarboplatin AUC 6ECOG PS 0Primary efficacy populationUnexpected safety signalsFirst-line treatmentPD-L1 statusPhase III studyPlatinum-based chemotherapyWT populationOverall survival analysisDeclaration of HelsinkiAttractive treatment choiceAtezolizumab monotherapyAUC 5AUC 6CPI monotherapyECOG PSImmune 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 therapyFrontline immunotherapy for NSCLC — the tale of the tail
Chiang AC, Herbst RS. Frontline immunotherapy for NSCLC — the tale of the tail. Nature Reviews Clinical Oncology 2020, 17: 73-74. PMID: 31907372, DOI: 10.1038/s41571-019-0317-y.Peer-Reviewed Original Research
2019
LBA1 Clinical efficacy of atezolizumab (atezo) in biomarker subgroups by SP142, SP263 and 22C3 PD-L1 immunohistochemistry (IHC) assays and by blood tumour mutational burden (bTMB): Results from the IMpower110 study
Herbst R, de Marinis F, Giaccone G, Reinmuth N, Vergnenegre A, Barrios C, Morise M, Felip E, Andric Z, Geater S, Ozguroglu M, Mocci S, McCleland M, Zou W, Enquist I, Komatsubara K, Deng Y, Kuriki H, Spigel D, Jassem J. LBA1 Clinical efficacy of atezolizumab (atezo) in biomarker subgroups by SP142, SP263 and 22C3 PD-L1 immunohistochemistry (IHC) assays and by blood tumour mutational burden (bTMB): Results from the IMpower110 study. Annals Of Oncology 2019, 30: xi62-xi63. DOI: 10.1093/annonc/mdz453.Peer-Reviewed Original ResearchBlood tumor mutational burdenBiomarker-evaluable populationTumor proportion scorePD-L1Bristol-Myers SquibbClinical trialsF. Hoffmann-La RocheLecture feesAstra ZenecaBoehringer IngelheimHoffmann-La RocheOS HRBiomarker subgroupsPD-L1 IHC assaysPD-L1 immunohistochemistry assaysIHC assaysEli LillyPrincipal investigatorECOG PS 0Genentech/RochePD-L1 cutoffsSignificant OS improvementStage IV NSCLCAstellas PharmaTumor mutational burden