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
2021
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
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 baselineChemotherapy
2019
LBA4 Association of KRAS mutational status with response to pembrolizumab monotherapy given as first-line therapy for PD-L1-positive advanced non-squamous NSCLC in Keynote-042
Herbst R, Lopes G, Kowalski D, Kasahara K, Wu Y, De Castro G, Cho B, Turna H, Cristescu R, Aurora-Garg D, Lunceford J, Kobie J, Ayers M, Pietanza M, Piperdi B, Mok T. LBA4 Association of KRAS mutational status with response to pembrolizumab monotherapy given as first-line therapy for PD-L1-positive advanced non-squamous NSCLC in Keynote-042. Annals Of Oncology 2019, 30: xi63-xi64. DOI: 10.1093/annonc/mdz453.001.Peer-Reviewed Original ResearchTumor mutational burdenNon-squamous NSCLCKRAS mutational statusAdvanced non-squamous NSCLCFirst-line therapyWhole-exome sequencingKRAS mutationsPembrolizumab monotherapyPD-L1Mutational statusSubsidiary of MerckBoehringer IngelheimMerck SharpBristol-Myers SquibbDohme Corp.Merck SeronoStandard first-line treatment optionFirst-line treatment optionEli LillyAdvanced PD-L1Genentech/RocheNon-squamous histologyPD-L1 TPSPD-L1 expressionFirst-line treatmentBiomarker-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 monotherapy
2017
Estimating long-term survival of PD-L1-expressing, previously treated, non-small cell lung cancer patients who received pembrolizumab in KEYNOTE-001 and -010.
Hellmann M, Ma J, Garon E, Hui R, Gandhi L, Soria J, Anderson K, Lubiniecki G, Piperdi B, Herbst R. Estimating long-term survival of PD-L1-expressing, previously treated, non-small cell lung cancer patients who received pembrolizumab in KEYNOTE-001 and -010. Journal Of Clinical Oncology 2017, 35: 77-77. DOI: 10.1200/jco.2017.35.7_suppl.77.Peer-Reviewed Original ResearchNon-small cell lung cancerLong-term survival ratesLong-term survivalAdvanced non-small cell lung cancerKEYNOTE-001KEYNOTE-010PD-L1Survival rateOverall survivalLong-term benefitsLong-term survival modelsNon-small cell lung cancer patientsCell lung cancer patientsPercentage of patientsSurvival modelsCell lung cancerLung cancer patientsTreat populationDocetaxel armPembrolizumab monotherapyParametric survival modelsCancer patientsLung cancerPatientsSubsequent independent validation