2020
Atezolizumab 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 population
2012
Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours
Martin LP, Kozloff MF, Herbst RS, Samuel TA, Kim S, Rosbrook B, Tortorici M, Chen Y, Tarazi J, Olszanski AJ, Rado T, Starr A, Cohen RB. Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours. British Journal Of Cancer 2012, 107: 1268-1276. PMID: 22996612, PMCID: PMC3494424, DOI: 10.1038/bjc.2012.407.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsCommon treatment-related adverse eventsSolid tumorsTreatment-related adverse eventsAntitumour activitySelective second-generation inhibitorPhase ICo-administered agentsVascular endothelial growth factor receptorHand-foot syndromeEndothelial growth factor receptorHuman xenograft tumor modelsEfficacy of chemotherapyXenograft tumor modelMultiple tumor typesAxitinib pharmacokineticsCapecitabine pharmacokineticsGrowth factor receptorStable diseaseStarting doseAdverse eventsPartial responseComplete responseTreatment regimenDocetaxel exposure
2008
Dose Escalation of Gemcitabine Is Possible With Concurrent Chest Three-Dimensional Rather Than Two-Dimensional Radiotherapy: A Phase I Trial in Patients With Stage III Non–Small-Cell Lung Cancer
Zinner RG, Komaki R, Cox JD, Glisson BS, Pisters KM, Herbst RS, Kies M, Liao Z, Hong WK, Fossella FV. Dose Escalation of Gemcitabine Is Possible With Concurrent Chest Three-Dimensional Rather Than Two-Dimensional Radiotherapy: A Phase I Trial in Patients With Stage III Non–Small-Cell Lung Cancer. International Journal Of Radiation Oncology • Biology • Physics 2008, 73: 119-127. PMID: 18556142, DOI: 10.1016/j.ijrobp.2008.03.069.Peer-Reviewed Original ResearchMeSH KeywordsAbdomenAdultAgedAged, 80 and overAntimetabolites, AntineoplasticCarcinoma, Non-Small-Cell LungCombined Modality TherapyDeoxycytidineDose-Response Relationship, DrugDose-Response Relationship, RadiationFeasibility StudiesFemaleGemcitabineHumansLung NeoplasmsMaleMiddle AgedRadiation-Sensitizing AgentsRadiotherapy, ConformalTreatment OutcomeConceptsGrade 3 esophagitisDose of gemcitabineCell lung cancerTwo-dimensional radiotherapyLung cancerThree-dimensional conformal radiotherapySevere acute esophagitisWeekly gemcitabine concurrentCycles of gemcitabinePhase II doseStage III NSCLCDose-limiting toxicityPhase I trialThree-dimensional CRTChest radiotherapyConcurrent chestConcurrent radiotherapySevere esophagitisAcute esophagitisI trialDose escalationConformal radiotherapyEsophagitisApparent diseaseStage III
2006
Development and Validation of a Drug Activity Biomarker that Shows Target Inhibition in Cancer Patients Receiving Enzastaurin, a Novel Protein Kinase C-β Inhibitor
Green LJ, Marder P, Ray C, Cook CA, Jaken S, Musib LC, Herbst RS, Carducci M, Britten CD, Basche M, Eckhardt SG, Thornton D. Development and Validation of a Drug Activity Biomarker that Shows Target Inhibition in Cancer Patients Receiving Enzastaurin, a Novel Protein Kinase C-β Inhibitor. Clinical Cancer Research 2006, 12: 3408-3415. PMID: 16740765, DOI: 10.1158/1078-0432.ccr-05-2231.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkersCapecitabineCell Line, TumorClinical Trials, Phase I as TopicDeoxycytidineEnzyme ActivatorsEnzyme InhibitorsFlow CytometryFluorouracilFollow-Up StudiesHumansIndolesLeukocytes, MononuclearMonocytesNeoplasmsProtein Kinase CProtein Kinase C betaReproducibility of ResultsSensitivity and SpecificitySignal TransductionStructure-Activity RelationshipTreatment OutcomeConceptsPeripheral blood mononuclear cellsDaily oral dosesBlood mononuclear cellsCancer patientsOral dosesMononuclear cellsFlow cytometryDrug activity biomarkerPKC activityTarget cellsActivity biomarkersPhorbol esterNormal donorsPatientsActivity of PKCU937 cell lineTarget inhibitionEnzastaurinKinase inhibitorsΒ inhibitorSignificant decreaseCell linesU937 cellsIntracellular phosphoproteinsProtein kinase C
2005
Phase I/IIa Study of Cetuximab With Gemcitabine Plus Carboplatin in Patients With Chemotherapy-Naïve Advanced Non–Small-Cell Lung Cancer
Robert F, Blumenschein G, Herbst RS, Fossella FV, Tseng J, Saleh MN, Needle M. Phase I/IIa Study of Cetuximab With Gemcitabine Plus Carboplatin in Patients With Chemotherapy-Naïve Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2005, 23: 9089-9096. PMID: 16301597, DOI: 10.1200/jco.2004.00.1438.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCarcinoma, Non-Small-Cell LungCetuximabDeoxycytidineDisease ProgressionDrug Administration ScheduleDrug EruptionsFemaleGemcitabineHumansInfusions, IntravenousLung NeoplasmsMaleMiddle AgedSurvival AnalysisTreatment OutcomeConceptsPhase I/IIa studyAdverse eventsIIa studyOverall survivalLung cancerToxicity profileResponse rateGrade 3 adverse eventsGrade 3 allergic reactionSmall cell lung cancerAcne-like rashMucositis/stomatitisCycles of therapyMedian overall survivalNausea/vomitingSafety/toxicity profileTumor response rateAcceptable toxicity profileFever/chillsCombination of cetuximabCell lung cancerAssessable patientsChemotherapy-naïveStable diseaseMedian survival
2004
Trastuzumab in combination with cisplatin and gemcitabine in patients with Her2-overexpressing, untreated, advanced non-small cell lung cancer: report of a phase II trial and findings regarding optimal identification of patients with Her2-overexpressing disease
Zinner RG, Glisson BS, Fossella FV, Pisters KM, Kies MS, Lee PM, Massarelli E, Sabloff B, Fritsche HA, Ro JY, Ordonez NG, Tran HT, Yang Y, Smith TL, Mass RD, Herbst RS. Trastuzumab in combination with cisplatin and gemcitabine in patients with Her2-overexpressing, untreated, advanced non-small cell lung cancer: report of a phase II trial and findings regarding optimal identification of patients with Her2-overexpressing disease. Lung Cancer 2004, 44: 99-110. PMID: 15013588, DOI: 10.1016/j.lungcan.2003.09.026.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerEnzyme-linked immunosorbent assayCell lung cancerSerum HER2Stage IIIBIHC 3Lung cancerHER2 scoreDay oneIHC analysisAdvanced non-small cell lung cancerPharmacokinetics of trastuzumabAddition of trastuzumabPhase II trialSerum enzyme-linked immunosorbent assayGemcitabine 1250Trastuzumab trialsChemonaive patientsII trialPartial responseHER2 overexpressingTrastuzumab therapyMedian timeAntigen levelsHER2 expressionGefitinib in Combination With Gemcitabine and Cisplatin in Advanced Non–Small-Cell Lung Cancer: A Phase III Trial—INTACT 1
Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, Natale RB, Schiller JH, von Pawel J, Pluzanska A, Gatzemeier U, Grous J, Ochs JS, Averbuch SD, Wolf MK, Rennie P, Fandi A, Johnson DH. Gefitinib in Combination With Gemcitabine and Cisplatin in Advanced Non–Small-Cell Lung Cancer: A Phase III Trial—INTACT 1. Journal Of Clinical Oncology 2004, 22: 777-784. PMID: 14990632, DOI: 10.1200/jco.2004.08.001.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCisplatinDeoxycytidineDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleFemaleGefitinibGemcitabineHumansLung NeoplasmsMaleMaximum Tolerated DoseMiddle AgedMultivariate AnalysisNeoplasm InvasivenessNeoplasm StagingProbabilityPrognosisQuinazolinesReference ValuesSurvival AnalysisTreatment OutcomeConceptsChemotherapy-naive patientsAdvanced NSCLCLung cancerAdvanced non-small cell lung cancerResponse rateNon-small cell lung cancerEpidermal growth factor receptor tyrosine kinase inhibitor gefitinibEnd pointUnresectable stage IIICycles of chemotherapyEfficacy end pointPhase II trialFirst-line gemcitabineTyrosine kinase inhibitor gefitinibPhase I trialCell lung cancerUnexpected adverse eventsMedian survival timeKinase inhibitor gefitinibFurther preclinical testingDaily gefitinibFavorable tolerabilityII trialPlacebo groupAdverse events
2002
The novel and effective nonplatinum, nontaxane combination of gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma
Herbst RS, Khuri FR, Lu C, Liu DD, Fossella FV, Glisson BS, Pisters KM, Shin DM, Papadimitrakopoulou VA, Kurie JM, Blumenschein G, Kies MS, Zinner R, Jung MS, Lu R, Lee JJ, Munden RF, Hong WK, Lee JS. The novel and effective nonplatinum, nontaxane combination of gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma. Cancer 2002, 95: 340-353. PMID: 12124835, DOI: 10.1002/cncr.10629.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntimetabolites, AntineoplasticAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsBiological TherapyCarcinoma, Non-Small-Cell LungCombined Modality TherapyDeoxycytidineDisease ProgressionFemaleGemcitabineHumansLung NeoplasmsMaleMiddle AgedSurvival RateVinblastineVinorelbineConceptsNonsmall cell lung carcinomaYear survival rateAdvanced nonsmall cell lung carcinomaThird-line therapyPhase II trialMedian survival timeCell lung carcinomaGrade 3Survival rateSignificant myelosuppressionStable diseaseII trialLung carcinomaSurvival timeStage IV nonsmall cell lung carcinomaDay 1Day 15Formal phase II trialCurrent phase II trialDose of vinorelbineGemcitabine/vinorelbineGrade 3 granulocytopeniaMedian performance statusMinimal grade 3Prior chemotherapy regimens
2001
Gemcitabine and vinorelbine in patients with advanced lung cancer: preclinical studies and report of a phase I trial
Herbst R, Lynch C, Vasconcelles M, Teicher B, Strauss G, Elias A, Anderson I, Zacarola P, Dang N, Leong T, Salgia R, Skarin A. Gemcitabine and vinorelbine in patients with advanced lung cancer: preclinical studies and report of a phase I trial. Cancer Chemotherapy And Pharmacology 2001, 48: 151-159. PMID: 11561781, DOI: 10.1007/s002800100282.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerAdvanced lung cancerDana-Farber Cancer InstituteLung cancerDose levelsMouse Lewis lung cancer modelLewis lung cancer modelMedian ECOG performance statusMouse Lewis lung carcinoma modelPhase I clinical studyDay 15 doseDose level 4ECOG performance statusLewis lung carcinoma modelCentral venous lineEfficacy of gemcitabinePhase I trialCell lung cancerLung cancer modelAbility of patientsHighest dose levelLung carcinoma modelHematologic toxicityChemotherapeutic regimenI trial
1999
Gemcitabine and vinorelbine combinations in the treatment of non-small cell lung cancer.
Herbst RS, Lilenbaum R. Gemcitabine and vinorelbine combinations in the treatment of non-small cell lung cancer. Seminars In Oncology 1999, 26: 67-70; discussion 71-2. PMID: 10585011.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced non-small cell lung cancerVinorelbine/gemcitabineCell lung cancerMedian survivalSurvival rateStable diseasePartial responseLung cancerDisease progressionDay 1Treatment of NSCLCStandard platinum-based regimensGemcitabine/vinorelbineChemotherapy-naive patientsPerformance status 0Treatment-naive patientsPhase II studyPlatinum-based regimensCombination of vinorelbineMedian survival timeOverall response rateNonplatinum agentsStatus 0Vinorelbine combination