Featured Publications
Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC
Tsuboi M, Herbst R, John T, Kato T, Majem M, Grohé C, Wang J, Goldman J, Lu S, Su W, de Marinis F, Shepherd F, Lee K, Le N, Dechaphunkul A, Kowalski D, Poole L, Bolanos A, Rukazenkov Y, Wu Y. Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. New England Journal Of Medicine 2023, 389: 137-147. PMID: 37272535, DOI: 10.1056/nejmoa2304594.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCOVID-19ErbB ReceptorsHumansLung NeoplasmsMutationNeoplasm Recurrence, LocalSurvival AnalysisConceptsDisease-free survivalOverall survivalIIIA diseaseStage IBAdjuvant osimertinibPlacebo groupOsimertinib groupNew serious adverse eventsSignificant overall survival benefitStage IILonger disease-free survivalEnd pointData cutoff datePrevious adjuvant chemotherapyDouble-blind trialOverall survival benefitPrimary end pointSecondary end pointsSerious adverse eventsCell lung cancerCoronavirus disease 2019Epidermal growth factor receptorADAURA trialAdjuvant chemotherapyEligible patientsThe end of the beginning: progress and next steps in KRAS-mutant non-small-cell lung cancer
Goldberg S, Herbst R. The end of the beginning: progress and next steps in KRAS-mutant non-small-cell lung cancer. The Lancet 2023, 401: 706-707. PMID: 36774937, DOI: 10.1016/s0140-6736(23)00288-x.Peer-Reviewed Original ResearchCarcinoma, Non-Small-Cell LungHumansLung NeoplasmsMutationProto-Oncogene Proteins p21(ras)Signal TransductionFuture Directions in the Management of Non-Small Cell Lung Cancer Harboring Driver Mutations.
Herbst RS. Future Directions in the Management of Non-Small Cell Lung Cancer Harboring Driver Mutations. Oncology 2022, 36: 562-563. PMID: 36107783, DOI: 10.46883/2022.25920974.Peer-Reviewed Original ResearchAdenocarcinoma of LungAnaplastic Lymphoma KinaseCarcinoma, Non-Small-Cell LungHumansLung NeoplasmsMutation
2023
Understanding health-related quality of life measures used in early-stage non-small cell lung cancer clinical trials: A review
Majem M, Basch E, Cella D, Garon E, Herbst R, Leighl N. Understanding health-related quality of life measures used in early-stage non-small cell lung cancer clinical trials: A review. Lung Cancer 2023, 187: 107419. PMID: 38070301, DOI: 10.1016/j.lungcan.2023.107419.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungHumansLung NeoplasmsNeoplasm Recurrence, LocalQuality of LifeSmall Cell Lung CarcinomaConceptsNon-small cell lung cancerEarly-stage diseaseHealth-related qualityClinical trialsEarly-stage non-small cell lung cancerTreatment-related adverse effectsAppropriate HRQoL instrumentNSCLC clinical trialsCell lung cancerLong-term treatmentLung cancer clinical trialsCancer clinical researchCancer clinical trialsAdjuvant treatmentAdvanced diseaseHRQOL assessmentTreatment landscapeDisease recurrenceHRQoL instrumentsLung cancerDisease progressionLife measuresHRQoLNarrative reviewHealthcare professionalsNovel Approach to Accelerate Lung Cancer Research: Lung-MAP and the Potential of Public-Private Partnerships
Herbst R, Blanke C, Sigal E. Novel Approach to Accelerate Lung Cancer Research: Lung-MAP and the Potential of Public-Private Partnerships. Clinical Cancer Research 2023, 30: 29-32. PMID: 37903180, PMCID: PMC10767300, DOI: 10.1158/1078-0432.ccr-23-2690.Peer-Reviewed Original ResearchOsimertinib in Resected EGFR-Mutated NSCLC. Reply.
Tsuboi M, Herbst R, Wu Y. Osimertinib in Resected EGFR-Mutated NSCLC. Reply. New England Journal Of Medicine 2023, 389: 1342. PMID: 37792623, DOI: 10.1056/nejmc2309385.Peer-Reviewed Original ResearchRepresentativeness of Patients Enrolled in the Lung Cancer Master Protocol (Lung-MAP).
Vaidya R, Unger J, Qian L, Minichiello K, Herbst R, Gandara D, Neal J, Leal T, Patel J, Dragnev K, Waqar S, Edelman M, Sigal E, Adam S, Malik S, Blanke C, LeBlanc M, Kelly K, Gray J, Redman M. Representativeness of Patients Enrolled in the Lung Cancer Master Protocol (Lung-MAP). JCO Precision Oncology 2023, 7: e2300218. PMID: 37677122, PMCID: PMC10581630, DOI: 10.1200/po.23.00218.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungFemaleHumansLungLung NeoplasmsMaleMolecular Targeted TherapyPatientsUnited StatesConceptsCharacteristics of patientsLung-MAPMaster protocolsNSCLC populationCell lung cancer trialsSEER registry dataPatients 65 yearsPrecision medicine clinical trialsPatient exclusion criteriaLung cancer trialsRepresentativeness of patientsMedicine clinical trialsNSCLC trialsOlder patientsMedicaid/More patientsSubgroup analysisCancer trialsClinical trialsVulnerable patientsRegistry dataExclusion criteriaPatientsNSCLC studiesSociodemographic characteristicsBiomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results
Gutierrez M, Lam W, Hellmann M, Gubens M, Aggarwal C, Tan D, Felip E, Chiu J, Lee J, Yang J, Garon E, Finocchiaro G, Ahn M, Luft A, Landers G, Basso A, Ma H, Kobie J, Palcza J, Cristescu R, Fong L, Snyder A, Yuan J, Herbst R. Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Nature Medicine 2023, 29: 1718-1727. PMID: 37429923, DOI: 10.1038/s41591-023-02385-6.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerObjective response rateAdvanced non-small cell lung cancerCell lung cancerSafety profileCombination therapyLung cancerInvestigator-assessed objective response rateRandomized phase 2 studySolid Tumors version 1.1T-cell-inflamed gene expression profileGroup IIIBiomarker-defined subgroupsFirst-line pembrolizumabPhase 2 studyProgression-free survivalResponse Evaluation CriteriaSubset of patientsHeterogenous tumor microenvironmentData cutoffOverall survivalSecondary outcomesPrimary outcomeTreatment armsTMB assessmentThree-Year Safety, Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial
John T, Grohé C, Goldman J, Shepherd F, de Marinis F, Kato T, Wang Q, Su W, Choi J, Sriuranpong V, Melotti B, Fidler M, Chen J, Albayaty M, Stachowiak M, Taggart S, Wu Y, Tsuboi M, Herbst R, Majem M. Three-Year Safety, Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial. Journal Of Thoracic Oncology 2023, 18: 1209-1221. PMID: 37236398, DOI: 10.1016/j.jtho.2023.05.015.Peer-Reviewed Original ResearchMeSH KeywordsAniline CompoundsCarcinoma, Non-Small-Cell LungErbB ReceptorsHumansLung NeoplasmsMutationProtein Kinase InhibitorsQuality of LifeConceptsThree-year safetyAdverse eventsAdjuvant osimertinibStage IBWeek 12Treatment completionCommon adverse eventsMost adverse eventsResected stage IBSignificant efficacy benefitDisease-free survivalNew safety signalsSF-36 surveyHealth-related qualityInterstitial lung diseaseMental component summaryTotal exposure durationADAURA trialWeek 24Component summaryEfficacy benefitsOsimertinib treatmentSF-36Lung diseaseSafety signalsGenomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer
Ravi A, Hellmann M, Arniella M, Holton M, Freeman S, Naranbhai V, Stewart C, Leshchiner I, Kim J, Akiyama Y, Griffin A, Vokes N, Sakhi M, Kamesan V, Rizvi H, Ricciuti B, Forde P, Anagnostou V, Riess J, Gibbons D, Pennell N, Velcheti V, Digumarthy S, Mino-Kenudson M, Califano A, Heymach J, Herbst R, Brahmer J, Schalper K, Velculescu V, Henick B, Rizvi N, Jänne P, Awad M, Chow A, Greenbaum B, Luksza M, Shaw A, Wolchok J, Hacohen N, Getz G, Gainor J. Genomic and transcriptomic analysis of checkpoint blockade response in advanced non-small cell lung cancer. Nature Genetics 2023, 55: 807-819. PMID: 37024582, PMCID: PMC10181943, DOI: 10.1038/s41588-023-01355-5.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungGenomicsHumansLung NeoplasmsProgrammed Cell Death 1 ReceptorTranscriptomeConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerCell lung cancerLung cancerAnti-PD-1/PD-L1 agentsCheckpoint blockade responsePD-L1 agentsTumor intrinsic subtypesCheckpoint inhibitorsCheckpoint blockadeTreatment landscapeImmunotherapy outcomesBlockade responseCohortBiological determinantsGenomic subgroupsEnhanced responseMolecular featuresWhole exomeCancerProminent associationOutcomesAssociationResponseNumber of associationsNovel Approaches for Dynamic Visualization of Adverse Event Data in Oncology Clinical Trials: A Case Study Using Immunotherapy Trial S1400-I (SWOG).
Lee S, Fan W, Wang A, Vaidya R, Redman M, Gettinger S, Bazhenova L, Herbst R, Hershman D, Unger J. Novel Approaches for Dynamic Visualization of Adverse Event Data in Oncology Clinical Trials: A Case Study Using Immunotherapy Trial S1400-I (SWOG). JCO Clinical Cancer Informatics 2023, 7: e2200165. PMID: 37084329, PMCID: PMC10281446, DOI: 10.1200/cci.22.00165.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungHumansImmunotherapyIpilimumabLung NeoplasmsNivolumabConceptsSystem organ classAdverse event dataRandomized phase III trialPhase III trialsCell lung cancerOncology clinical trialsOverall toxicity profileIII trialsNeurologic toxicityTreatment armsCardiac toxicityLung cancerClinical trialsGrade 3High prevalenceOrgan classToxicity profileNivolumabTreatment groupsStage IVEndocrine toxicityType of AEToxicity typesAE termsIpilimumabAdjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non–Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial
Herbst R, Wu Y, John T, Grohe C, Majem M, Wang J, Kato T, Goldman J, Laktionov K, Kim S, Yu C, Vu H, Lu S, Lee K, Mukhametshina G, Akewanlop C, de Marinis F, Bonanno L, Domine M, Shepherd F, Urban D, Huang X, Bolanos A, Stachowiak M, Tsuboi M. Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non–Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial. Journal Of Clinical Oncology 2023, 41: 1830-1840. PMID: 36720083, PMCID: PMC10082285, DOI: 10.1200/jco.22.02186.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAntineoplastic AgentsCarcinoma, Non-Small-Cell LungChemotherapy, AdjuvantDouble-Blind MethodErbB ReceptorsHumansLung NeoplasmsMutationNeoplasm StagingConceptsII-IIIA diseaseStage IB-IIIAAdjuvant osimertinibDFS HRDFS ratesDistant recurrenceEnd pointSafety profileLung cancerSignificant disease-free survival benefitPrimary analysisDisease-free survival benefitLong-term safety profileSmall cell lung cancerStratified log-rank testExploratory end pointsPrimary end pointSecondary end pointsConsistent safety profilePatterns of recurrenceCell lung cancerComplete tumor resectionLog-rank testADAURA trialData cutoffAssociations 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 analysisQuality-of-life outcomes and risk prediction for patients randomized to nivolumab plus ipilimumab vs nivolumab on LungMAP-S1400I
Unger J, Qian L, Redman M, Tavernier S, Minasian L, Sigal E, Papadimitrakopoulou V, Leblanc M, Cleeland C, Dzingle S, Summers T, Chao H, Madhusudhana S, Villaruz L, Crawford J, Gray J, Kelly K, Gandara D, Bazhenova L, Herbst R, Gettinger S, Moinpour C. Quality-of-life outcomes and risk prediction for patients randomized to nivolumab plus ipilimumab vs nivolumab on LungMAP-S1400I. Journal Of The National Cancer Institute 2023, 115: 437-446. PMID: 36625510, PMCID: PMC10086628, DOI: 10.1093/jnci/djad003.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungFemaleHumansIpilimumabLung NeoplasmsMaleNivolumabQuality of LifeConceptsQuality of lifeComposite risk modelAppetite lossSeverity scoreWeek 13Advanced squamous cell lung cancerWeek 7Baseline patient-reported outcomesRandomized phase III trialSquamous cell lung cancerPhase III trialsRisk of progressionShortness of breathCell lung cancerPatient-reported outcomesRisk of deathMultivariable linear regressionEffect of treatmentEvaluable patientsPrimary endpointIII trialsOverall survivalMedian ageAdvanced cancerPrognostic relevance
2022
BFAST 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 tumorsBiomarkersCancerBurdenPembrolizumabNSCLCPatientsTumorsTrialsQuantitative 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 ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungHumansHyaluronan ReceptorsLung NeoplasmsProgrammed Cell Death 1 ReceptorProteomicsConceptsProgression-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 cohortAddressing 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 ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungC-Mer Tyrosine KinaseHumansLung NeoplasmsProgrammed Cell Death 1 ReceptorTumor MicroenvironmentConceptsImmunosuppressive 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 NSCLCQuantitative tissue analysis and role of myeloid cells in non-small cell lung cancer
Henick BS, Villarroel-Espindola F, Datar I, Sanmamed MF, Yu J, Desai S, Li A, Aguirre-Ducler A, Syrigos K, Rimm DL, Chen L, Herbst RS, Schalper KA. Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e005025. PMID: 35793873, PMCID: PMC9260844, DOI: 10.1136/jitc-2022-005025.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellHLA-DR AntigensHumansLung NeoplasmsMyeloid CellsRetrospective StudiesConceptsNon-small cell lung cancerSquamous cell carcinomaHuman non-small cell lung cancerMyeloid cell subsetsCell lung cancerHLA-DRLung adenocarcinomaMyeloid cellsCell subsetsLung cancerLung tissueQuantitative immunofluorescenceNon-tumor lung tissuesIndependent NSCLC cohortsLevels of CD68Multiplexed quantitative immunofluorescenceProinflammatory myeloid cellsHLA-DR expressionM1-like macrophagesImmature myeloid cell populationMyeloid cell populationsKRAS mutant tumorsNormal lung tissuesTumor epithelial cellsNon-tumor lungProgrammed 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 ResearchMeSH KeywordsB7-H1 AntigenCarcinoma, Non-Small-Cell LungHumansImmunotherapyLigandsLung NeoplasmsPredictive Value of TestsReal-Time Polymerase Chain ReactionRetrospective StudiesRNA, MessengerConceptsImmune 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 NSCLC