2022
Addressing 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 NSCLCSociety 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 disordersANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA
Remon J, Lacas B, Herbst R, Reck M, Garon EB, Scagliotti GV, Ramlau R, Hanna N, Vansteenkiste J, Yoh K, Groen HJM, Heymach JV, Mandrekar SJ, Okamoto I, Neal JW, Heist RS, Planchard D, Pignon JP, Besse B, group A, Besse B, Lacas B, Pignon J, Remon J, Berghmans T, Dahlberg S, Felip E, Berghmans T, Besse B, Dahlberg S, Felip E, Garon E, Groen H, Hanna N, Heist R, Herbst R, Heymach J, Lacas B, Adjei A, Heist R, Mandrekar S, Neal J, Okamoto I, Pignon J, Ramlau R, Remon J, Reck M, Scagliotti G, Vansteenkiste J, Yoh K. ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA. European Journal Of Cancer 2022, 166: 112-125. PMID: 35286903, DOI: 10.1016/j.ejca.2022.02.002.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerProgression-free survivalAdvanced non-small cell lung cancerFirst-line therapyCell lung cancerIndividual patient dataHazard ratioYounger patientsLung cancerPulmonary thromboembolic eventsPatient dataSecond-line treatmentFirst-line treatmentRisk of hypertensionFixed-effects modelOS benefitPFS benefitThromboembolic eventsOverall survivalSubgroup analysisAntiangiogenicsMeta-AnalysisPatientsMedical needChemotherapy
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 statusSelecting 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
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 signals
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 treatmentImmunotherapy 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 workBiomarkersSurvival
2010
Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial
Herbst RS, Sun Y, Eberhardt W, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. The Lancet Oncology 2010, 11: 619-626. PMID: 20570559, PMCID: PMC3225192, DOI: 10.1016/s1470-2045(10)70132-7.Peer-Reviewed Original ResearchConceptsProgression-free survivalMedian progression-free survivalVascular endothelial growth factor receptorCell lung cancerEpidermal growth factor receptorVandetanib groupFebrile neutropeniaGrowth factor receptorPlacebo groupAdverse eventsLung cancerCommon serious adverse eventsDefinitive phase 3 trialLonger progression-free survivalComparison of PFSDaily oral inhibitorHigher adverse eventsSecond-line treatmentFirst-line chemotherapyFirst-line therapyPhase 2 studyPhase 3 trialSerious adverse eventsFactor receptorEndothelial growth factor receptor
2005
Phase II study of pemetrexed in combination with carboplatin in the first‐line treatment of advanced nonsmall cell lung cancer
Zinner RG, Fossella FV, Gladish GW, Glisson BS, Blumenschein GR, Papadimitrakopoulou VA, Pisters KM, Kim ES, Oh YW, Peeples BO, Ye Z, Curiel RE, Obasaju CK, Hong WK, Herbst RS. Phase II study of pemetrexed in combination with carboplatin in the first‐line treatment of advanced nonsmall cell lung cancer. Cancer 2005, 104: 2449-2456. PMID: 16258975, DOI: 10.1002/cncr.21480.Peer-Reviewed Original ResearchConceptsAdvanced nonsmall cell lung cancerNonsmall cell lung cancerCell lung cancerPerformance statusLung cancerSerum concentration-time curveGrade 3/4 thrombocytopeniaNonhematologic side effectsZubrod performance statusGrade 3/4 neutropeniaPartial response ratePercent of patientsPhase II studyStage IV diseaseFirst-line therapyFirst-line treatmentConcentration-time curveCarboplatin areaPrior chemotherapyStage IIIBII studyMedian ageMedian timeSensory neuropathyMedian number
2004
Pemetrexed in the Treatment of Advanced Non–Small-Cell Lung Cancer: A Review of the Clinical Data
Zinner RG, Herbst RS. Pemetrexed in the Treatment of Advanced Non–Small-Cell Lung Cancer: A Review of the Clinical Data. Clinical Lung Cancer 2004, 5: s67-s74. PMID: 15117428, DOI: 10.3816/clc.2004.s.006.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSecond-line activityPhase III trialsIII trialsLung cancerAdvanced non-small cell lung cancerPhase II studyFirst-line therapyCell lung cancerFavorable toxicity profileChest radiationII studyThoracic malignanciesClinical dataSignificant efficacyToxicity profileSide effectsUseful agentFDA approvalPemetrexedPhase ICisplatinTrialsFurther studiesMesothelioma