2024
SWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer.
Reckamp K, Redman M, Dragnev K, Iams W, Henick B, Miao J, LeBlanc M, Carrizosa D, Herbst R, Blanke C, Gray J. SWOG S2302, PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (PR) versus standard of care (SOC) for participants previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer. Journal Of Clinical Oncology 2024, 42: tps8657-tps8657. DOI: 10.1200/jco.2024.42.16_suppl.tps8657.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerStandard of careCell lung cancerPD-(L)1Overall survivalAdverse eventsRecurrent non-small cell lung cancerLung cancerTreatment-related adverse eventsRandomized phase II trialStandard of care treatmentPlatinum-based therapyTreated with immunotherapyPhase II trialLog-rank testCompare OSInhibitor therapyII trialCombination therapyStatistically significant improvementTumor resistanceSafety profileTherapeutic optionsRandomized study
2023
SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei H, de Marinis F, Dumoulin D, Reynolds C, Theelen W, Percent I, Calderon V, Johnson M, Madroszyk-Flandin A, Garon E, He K, Planchard D, Reck M, Popat S, Herbst R, Leal T, Shazer R, Yan X, Harrigan R, Peters S, Investigators S, Abdel-Karim I, Abdelsalam M, Addeo A, Aguado C, Alexander P, Alt J, Azzi G, Balaraman R, Biesma B, Blackhall F, Bohnet S, Boleti E, Borghaei H, Bradbury P, Brighenti M, Campbell N, Campbell T, Canon J, Cappuzzo F, Costa E, Cavanna L, Cetnar J, Chella A, Chouaid C, Christoph D, Castán J, Dakhil S, de Castro Carpeño F, de Marinis F, Delmonte A, Demedts I, Demey W, Dits J, del Pilar Diz Taín M, Gómez M, Dorius T, Dumoulin D, Duruisseaux M, Eaton K, González E, Evans D, Faehling M, Farrell N, Feinstein T, Font E, Campelo M, Garon E, López M, Germonpré P, Gersten T, Cao M, Gopaluni S, Greillier L, Grossi F, Guisier F, Gurubhagavatula S, Calderón V, Hakimian D, Hall R, Hao D, Harris R, Hashemi S, He K, Hendriks L, Huang C, Ibrahim E, Jain S, Johnson M, Jones B, Jones M, Vidal Ó, Juergens R, Kaderbhai C, Kastelijn E, Keresztes R, Kio E, Kokowski K, Konduri K, Kulkarni S, Kuon J, Kurkjian C, Labbé C, Lerner R, Lim F, Madroszyk-Flandin A, Marathe O, Martincic D, McClay E, McIntyre K, Mekhail T, Misino A, Molinier O, Morabito A, Morócz É, Müller V, Nagy T, Nguyen A, Nidhiry E, Okazaki I, Ortega-Granados A, Ostoros G, Oubre D, Owen S, Pachipala K, Park D, Patel P, Percent I, Pérol M, Peters S, Piet B, Planchard D, Polychronis A, Aix S, Pons-Tostivint E, Popat S, Pulla M, Quantin X, Quéré G, Rafique N, Ramaekers R, Reck M, Reiman A, Reinmuth N, Reynolds C, Rodríguez-Abreu D, Romano G, Roque T, Salzberg M, Sanborn R, Sandiego S, Schaefer E, Schreeder M, Seetharamu N, Seneviratne L, Shah P, Shunyakov L, Slater D, Parra H, Stigt J, Stilwill J, Su J, Surmont V, Swink A, Szalai Z, Talbot T, Garcia A, Theelen W, Thompson J, Tiseo M, Uprety D, Uyeki J, van der Leest K, Van Ho A, van Putten J, Estévez S, Veatch A, Vergnenègre A, Ward P, Weise A, Weiss M, Whitehurst M, Zai S, Zalcman G, Zuniga R. SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. Annals Of Oncology 2023, 35: 66-76. PMID: 37866811, DOI: 10.1016/j.annonc.2023.10.004.Peer-Reviewed Original ResearchClinical benefit rateObjective response rateProgression-free survivalCell lung cancerOverall survivalNonsquamous NSCLCPrimary endpointLung cancerMedian progression-free survivalTreatment-related adverse eventsReceptor tyrosine kinase inhibitorsAdvanced nonsquamous NSCLCCheckpoint inhibitor therapyMedian overall survivalPlatinum-based chemotherapyDuration of responseImmunosuppressive tumor microenvironmentTyrosine kinase inhibitorsImmunostimulatory stateMedian DoRSecondary endpointsMost patientsAdverse eventsInhibitor therapySafety profileBiomarker-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 assessmentAdjuvant 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 ResearchConceptsII-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 cutoff
2020
Osimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA.
Herbst R, Tsuboi M, John T, Grohé C, Majem M, Goldman J, Kim S, Marmol D, Rukazenkov Y, Wu Y. Osimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. Journal Of Clinical Oncology 2020, 38: lba5-lba5. DOI: 10.1200/jco.2020.38.18_suppl.lba5.Peer-Reviewed Original ResearchDisease-free survivalComplete tumor resectionDFS hazard ratioAdjuvant chemotherapyData cutoffHazard ratioOverall survivalTumor resectionAdjuvant osimertinibDFS ratesEGFRm NSCLCEGFR-TKISafety profileEGFR mutation-positive NSCLCEffective new treatment strategyResected stage IISafety of osimertinibEarly-stage diseaseMutation-positive NSCLCNew treatment strategiesUnplanned interim analysisEligible ptsIIIA NSCLCNSCLC presentPS 0/1IMpower110: Clinical safety in a phase III study of atezolizumab (atezo) monotherapy (mono) vs platinum-based chemotherapy (chemo) in first-line non-small cell lung cancer (NSCLC).
Jassem J, Herbst R, de Marinis F, Cadranel J, Csőszi T, Isla D, Chen G, Syrigos K, Cortinovis D, Hida T, Mocci S, Phan S, Enquist I, Patel H, Villalobos M, Wen X, Deng Y, Kuriki H, Spigel D, Giaccone G. IMpower110: Clinical safety in a phase III study of atezolizumab (atezo) monotherapy (mono) vs platinum-based chemotherapy (chemo) in first-line non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2020, 38: e21623-e21623. DOI: 10.1200/jco.2020.38.15_suppl.e21623.Peer-Reviewed Original ResearchNon-small cell lung cancerPD-L1 expressionSafety profileFirst‐line non‐small cell lung cancerCarboplatin AUC 6ECOG PS 0NCI CTCAE v4.0Chemo-naive patientsNew safety signalsPhase III studyPlatinum-based chemotherapyFavorable safety profileCell lung cancerAtezolizumab monotherapyAUC 5AUC 6Gemcitabine 1250Endocrine therapySystemic glucocorticoidsCTCAE v4.0Data cutoffIII studyPS 0PD-L1GEM 1000
2011
A Phase I study to assess the safety, tolerability, and pharmacokinetics of AZD4877, an intravenous Eg5 inhibitor in patients with advanced solid tumors
Infante JR, Kurzrock R, Spratlin J, Burris HA, Eckhardt SG, Li J, Wu K, Skolnik JM, Hylander-Gans L, Osmukhina A, Huszar D, Herbst RS. A Phase I study to assess the safety, tolerability, and pharmacokinetics of AZD4877, an intravenous Eg5 inhibitor in patients with advanced solid tumors. Cancer Chemotherapy And Pharmacology 2011, 69: 165-172. PMID: 21638123, DOI: 10.1007/s00280-011-1667-z.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPrimary dose-limiting toxicityPhase IAcceptable safety profileAdvanced solid malignanciesAdvanced solid tumorsRelated adverse eventsSeverity of neutropeniaConclusionThe MTDAdverse eventsIntravenous infusionSafety profileSolid malignanciesAZD4877Intermediate doseDose reductionPart BPharmacokinetic profileDay 1Solid tumorsPart ANeutropeniaTolerabilityPatientsMTD
2009
Safety, Pharmacokinetics, and Antitumor Activity of AMG 386, a Selective Angiopoietin Inhibitor, in Adult Patients With Advanced Solid Tumors
Herbst RS, Hong D, Chap L, Kurzrock R, Jackson E, Silverman JM, Rasmussen E, Sun YN, Zhong D, Hwang YC, Evelhoch JL, Oliner JD, Le N, Rosen LS. Safety, Pharmacokinetics, and Antitumor Activity of AMG 386, a Selective Angiopoietin Inhibitor, in Adult Patients With Advanced Solid Tumors. Journal Of Clinical Oncology 2009, 27: 3557-3565. PMID: 19546406, DOI: 10.1200/jco.2008.19.6683.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAngiopoietinsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntimetabolites, AntineoplasticBevacizumabDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFatigueFemaleHumansInfusions, IntravenousMaleMaximum Tolerated DoseMiddle AgedNeoplasm StagingNeoplasmsTreatment OutcomeConceptsAMG 386Advanced solid tumorsPartial responseAntitumor activitySolid tumorsElimination half-life valuesPatients 48 hoursMaximum-tolerated doseTreatment-related toxicityDose-limiting toxicityRefractory ovarian cancerWeeks of treatmentPeptide-Fc fusion proteinVolume transfer constantAngiopoietin inhibitorsCommon toxicitiesStable diseasePeripheral edemaAdult patientsClinical sequelaeMethods PatientsWeekly dosesTumor burdenRespiratory arrestSafety profile
2007
Enzastaurin, a Protein Kinase Cβ–Selective Inhibitor, and Its Potential Application as an Anticancer Agent in Lung Cancer
Herbst RS, Oh Y, Wagle A, Lahn M. Enzastaurin, a Protein Kinase Cβ–Selective Inhibitor, and Its Potential Application as an Anticancer Agent in Lung Cancer. Clinical Cancer Research 2007, 13: 4641s-4646s. PMID: 17671157, DOI: 10.1158/1078-0432.ccr-07-0538.Peer-Reviewed Original ResearchConceptsSerine/threonine kinase inhibitorLung cancerOral serine/threonine kinase inhibitorProtein kinase CFavorable safety profileCurrent phase IKinase CTumor cell apoptosisAkt pathwayClinical findingsSafety profilePKC inhibitorTumor-induced angiogenesisPreclinical experienceCell apoptosisEnzastaurinKinase inhibitorsPhase ICancer
2006
Multicenter Open-label Extension Trial of Long-term Treatment with Gefitinib (IRESSA®)
Nakagawa K, Ranson M, Yano S, Tamura T, Saka H, Imamura F, Yokoyama A, Matsui K, Jiang H, Herbst R. Multicenter Open-label Extension Trial of Long-term Treatment with Gefitinib (IRESSA®). Haigan 2006, 46: 345. DOI: 10.2482/haigan.46.345.Peer-Reviewed Original ResearchProgression-free survivalLong-term treatmentNew safety issuesExtension trialOpen-label extension trialSkin-related adverse eventsMedian overall survivalMajority of patientsLong-term safetyGefitinib monotherapyAdvanced NSCLCAdverse eventsOverall survivalParent trialClinical benefitGefitinib treatmentSafety profileClinical trialsClinical studiesPatientsGefitinibIdeal 1TrialsSafety issuesSurvival