2022
Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter
Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, Ansstas G, Baehring J, Taylor JW, Honnorat J, Petrecca K, De Vos F, Wick A, Sumrall A, Sahebjam S, Mellinghoff IK, Kinoshita M, Roberts M, Slepetis R, Warad D, Leung D, Lee M, Reardon DA, Omuro A. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro-Oncology 2022, 24: 1935-1949. PMID: 35511454, PMCID: PMC9629431, DOI: 10.1093/neuonc/noac116.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalMGMT promoterBaseline corticosteroidsTreatment-related adverse event ratesImmune checkpoint inhibitor nivolumabNew safety signalsPhase III trialsAdverse event ratesCheckpoint inhibitor nivolumabCare radiotherapyInhibitor nivolumabPrimary endpointIII trialsSame regimenExperience recurrenceNivolumabSafety signalsPlaceboPatientsRadiotherapyTemozolomideEvent ratesMonthsPhase IIIImmune-checkpoint inhibitors for glioblastoma: what have we learned?
Omuro A. Immune-checkpoint inhibitors for glioblastoma: what have we learned? Arquivos De Neuro-Psiquiatria 2022, 80: 266-269. PMID: 35976319, PMCID: PMC9491432, DOI: 10.1590/0004-282x-anp-2022-s129.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsRecurrent glioblastomaBrain tumorsRandomized phase 3 trialCommon malignant primary brain tumorPost-treatment tumor samplesMalignant primary brain tumorSuccessful immunotherapeutic approachesPhase 3 trialPhase 1 studySelection of patientsT cell dysfunctionNew safety concernsHigh mutational burdenPrimary brain tumorsCheckpoint inhibitorsRadiographic responseImmunotherapeutic approachesPD-L1Survival improvementImmunologic responseTherapeutic optionsClinical trialsCNS microenvironmentCell dysfunctionRadiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial
Omuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, Sumrall A, Baehring J, van den Bent M, Bähr O, Lombardi G, Mulholland P, Tabatabai G, Lassen U, Sepulveda JM, Khasraw M, Vauleon E, Muragaki Y, Di Giacomo AM, Butowski N, Roth P, Qian X, Fu AZ, Liu Y, Potter V, Chalamandaris AG, Tatsuoka K, Lim M, Weller M. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro-Oncology 2022, 25: 123-134. PMID: 35419607, PMCID: PMC9825306, DOI: 10.1093/neuonc/noac099.Peer-Reviewed Original ResearchConceptsOverall survivalUnmethylated MGMT promoterMedian OSPrimary endpointInternational randomized phase III trialTreatment-related adverse event ratesMedian progression-free survivalRandomized phase III trialMGMT promoterEfficacy of nivolumabLonger median OSMedian overall survivalNew safety signalsProgression-free survivalAddition of temozolomideAdverse event ratesPhase III trialsUse of temozolomideStandard of careStudy treatment armsImproved OSIII trialsTreatment armsStandard radiotherapyNivolumab
2020
Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma
Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bähr O, Phuphanich S, Sepulveda JM, De Souza P, Sahebjam S, Carleton M, Tatsuoka K, Taitt C, Zwirtes R, Sampson J, Weller M. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma. JAMA Oncology 2020, 6: 1003-1010. PMID: 32437507, PMCID: PMC7243167, DOI: 10.1001/jamaoncol.2020.1024.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAntineoplastic Agents, ImmunologicalBevacizumabBrain NeoplasmsDNA Modification MethylasesDNA Repair EnzymesFemaleGlioblastomaHumansImmune Checkpoint InhibitorsMaleMiddle AgedNeoplasm Recurrence, LocalNivolumabProgrammed Cell Death 1 ReceptorTemozolomideTreatment OutcomeTumor Suppressor ProteinsYoung AdultConceptsTreatment-related adverse eventsPhase 3 clinical trialsPrimary end pointOverall survivalRecurrent glioblastomaClinical trialsMedian OSGrade 3/4 treatment-related adverse eventsRandomized phase 3 clinical trialSingle-agent PD-1 blockadeEnd pointEffects of nivolumabUnacceptable toxic effectsMedian overall survivalObjective response ratePD-1 blockadeOverall patient populationImmune checkpoint blockadeData cutoffAdverse eventsCheckpoint blockadeFirst recurrenceInhibitor therapyClinical outcomesSafety profile
2017
Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143
Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, Voloschin A, Ramkissoon SH, Ligon KL, Latek R, Zwirtes R, Strauss L, Paliwal P, Harbison CT, Reardon DA, Sampson JH. Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. Neuro-Oncology 2017, 20: 674-686. PMID: 29106665, PMCID: PMC5892140, DOI: 10.1093/neuonc/nox208.Peer-Reviewed Original ResearchConceptsAdverse eventsRecurrent glioblastomaCommon treatment-related adverse eventsTreatment-related adverse eventsDeath ligand 1 (PD-L1) expressionEffects of nivolumabExploratory efficacy outcomesSafety/tolerabilityFindings merit further investigationLigand 1 expressionCheckMate 143Ipilimumab doseNivolumab monotherapyStable diseaseAlternative regimenEfficacy outcomesRadiographic progressionMost patientsPartial responseNivolumabIpilimumabMerit further investigationPatientsI cohortFurther evaluation