2023
Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC ☆
Mok T, Lopes G, Cho B, Kowalski D, Kasahara K, Wu Y, de Castro G, Turna H, Cristescu R, Aurora-Garg D, Loboda A, Lunceford J, Kobie J, Ayers M, Pietanza M, Piperdi B, Herbst R. Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC ☆. Annals Of Oncology 2023, 34: 377-388. PMID: 36709038, DOI: 10.1016/j.annonc.2023.01.011.Peer-Reviewed Original ResearchConceptsTissue tumor mutational burdenImproved overall survivalProgression-free survivalTumor mutational burdenOverall survivalKEYNOTE-042Pembrolizumab monotherapyKRAS mutationsClinical utilityMutational burdenMutation statusPD-L1 tumor proportion scoreStandard first-line treatmentEGFR/ALK alterationsAdvanced PD-L1First-line treatmentPD-L1 expressionTumor proportion scorePlatinum-based chemotherapyDeath ligand 1Cell lung cancerPotential predictive biomarkersCut pointsKRAS mutation statusRetrospective exploratory analysis
2022
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
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 cohort
2021
Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1–Positive Advanced NSCLC
Herbst RS, Garon EB, Kim DW, Cho BC, Gervais R, Perez-Gracia JL, Han JY, Majem M, Forster MD, Monnet I, Novello S, Gubens MA, Boyer M, Su WC, Samkari A, Jensen EH, Kobie J, Piperdi B, Baas P. Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1–Positive Advanced NSCLC. Journal Of Thoracic Oncology 2021, 16: 1718-1732. PMID: 34048946, DOI: 10.1016/j.jtho.2021.05.001.Peer-Reviewed Original ResearchConceptsPD-L1 tumor proportion scoreTumor proportion scoreAdvanced NSCLCOverall survivalPembrolizumab improved overall survivalTissue tumor mutational burdenExploratory biomarker analysisImproved overall survivalProgrammed Death LigandTumor mutational burdenDocetaxel 75KEYNOTE-010Pembrolizumab dosesPembrolizumab treatmentSurvival updateData cutoffObjective responseHazard ratioOS ratesCare treatmentLong-term benefitsMedian studyImproved outcomesPembrolizumabProportion score
2020
Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC
Herbst RS, Arkenau HT, Bendell J, Arrowsmith E, Wermke M, Soriano A, Penel N, Santana-Davila R, Bischoff H, Chau I, Mi G, Wang H, Rasmussen E, Ferry D, Chao BH, Paz-Ares L. Phase 1 Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. Journal Of Thoracic Oncology 2020, 16: 289-298. PMID: 33068794, DOI: 10.1016/j.jtho.2020.10.004.Peer-Reviewed Original ResearchConceptsProgression-free survivalTumor proportion scoreMedian progression-free survivalTreatment-related adverse eventsPD-L1 expressionT-cell signatureCD274 gene expressionAdverse eventsPhase 1a/b trialPD-L1 tumor proportion scoreHigh PD-L1 expressionManageable safety profileMedian overall survivalObjective response ratePD-L1 positivityFirst-line therapyOverall survival ratePD-L1 immunohistochemistryCohort EPembrolizumab treatmentPFS ratesExpansion cohortClinical responseOverall survivalEfficacy signalsLong-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study.
Herbst RS, Garon EB, Kim DW, Cho BC, Perez-Gracia JL, Han JY, Arvis CD, Majem M, Forster MD, Monnet I, Novello S, Szalai Z, Gubens MA, Su WC, Ceresoli GL, Samkari A, Jensen EH, Lubiniecki GM, Baas P. Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study. Journal Of Clinical Oncology 2020, 38: 1580-1590. PMID: 32078391, DOI: 10.1200/jco.19.02446.Peer-Reviewed Original ResearchConceptsTumor proportion scoreTreatment-related adverse eventsSecond-course treatmentOverall survivalAdverse eventsLung cancerGrade 3Advanced non-small cell lung cancerPD-L1 tumor proportion scoreNon-small cell lung cancerLong-term OS benefitPembrolizumab improved overall survivalProgression-free survival ratesProgrammed Death Ligand 1Improved overall survivalDeath ligand 1Cell lung cancerLong-term outcomesYears of treatmentOS benefitPembrolizumab dosesStable diseaseAdvanced NSCLCEligible patientsDurable responses
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 burdenRandomized, double-blind, phase 3 trial of first-line pembrolizumab + platinum doublet chemotherapy (chemo) ± lenvatinib in patients (pts) with metastatic nonsquamous non–small-cell lung cancer (NSCLC): LEAP-006.
Hui R, Nishio M, Reck M, Rodriguez-Abreu D, Fouad T, Flaim D, Yin L, Dang T, Herbst R. Randomized, double-blind, phase 3 trial of first-line pembrolizumab + platinum doublet chemotherapy (chemo) ± lenvatinib in patients (pts) with metastatic nonsquamous non–small-cell lung cancer (NSCLC): LEAP-006. Journal Of Clinical Oncology 2019, 37: tps9118-tps9118. DOI: 10.1200/jco.2019.37.15_suppl.tps9118.Peer-Reviewed Original ResearchPrimary endpointPD-L1 tumor proportion scoreFirst-line lenvatinibMetastatic nonsquamous NSCLCNCI CTCAE v4.0Platinum-doublet chemotherapyFirst-line pembrolizumabPhase 3 trialTumor proportion scoreDose-limiting toxicityKaplan-Meier methodCell lung cancerLog-rank testQuality of lifeDoublet chemotherapyECOG PSMaintenance pembrolizumabAdvanced NSCLCNonsquamous NSCLCSecondary endpointsStudy withdrawalCTCAE v4.0Carboplatin AUCNew cancer therapiesLung cancerUse of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial
Herbst RS, Baas P, Perez-Gracia JL, Felip E, Kim D, Han J, Molina JR, Kim J, Arvis C, Ahn M, Majem M, Fidler MJ, Surmont V, de Castro G, Garrido M, Shentu Y, Emancipator K, Samkari A, Jensen EH, Lubiniecki GM, Garon EB. Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Annals Of Oncology 2019, 30: 281-289. PMID: 30657853, PMCID: PMC6931268, DOI: 10.1093/annonc/mdy545.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiopsyCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellDocetaxelFemaleFollow-Up StudiesHumansInternational AgenciesLung NeoplasmsMaleMiddle AgedParaffin EmbeddingPrognosisSpecimen HandlingSurvival RateYoung AdultConceptsTumor proportion scoreOS hazard ratioPD-L1 expressionProgression-free survivalPFS hazard ratioHazard ratioOverall survivalTumor samplesPD-L1PD-L1 tumor proportion scorePrespecified exploratory analysisPrimary end pointSubset of patientsCell lung cancerDeath 1 proteinArchival samplesDocetaxel 75KEYNOTE-010Pembrolizumab dosesRECIST v1.1Advanced NSCLCLung cancerProportion scorePatientsPrimary analysis
2016
Pembrolizumab vs docetaxel for previously treated advanced NSCLC with a PD-L1 tumor proportion score (TPS) 1%-49%: Results from KEYNOTE-010.
Garon E, Herbst R, Kim D, Felip E, Perez-Gracia J, Han J, Molina J, Kim J, Dubos Arvis C, Ahn M, Majem M, Fidler M, Gubens M, Castro G, Garrido M, Shentu Y, Im E, Lubiniecki G, Baas P. Pembrolizumab vs docetaxel for previously treated advanced NSCLC with a PD-L1 tumor proportion score (TPS) 1%-49%: Results from KEYNOTE-010. Journal Of Clinical Oncology 2016, 34: 9024-9024. DOI: 10.1200/jco.2016.34.15_suppl.9024.Peer-Reviewed Original ResearchTumor proportion scorePD-L1 tumor proportion scoreKEYNOTE-010Advanced NSCLCProportion scoreNSCLCDocetaxel