2022
Radiotherapy 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 radiotherapyNivolumabNivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143
Omuro A, Reardon DA, Sampson JH, Baehring J, Sahebjam S, Cloughesy TF, Chalamandaris AG, Potter V, Butowski N, Lim M. Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143. Neuro-Oncology Advances 2022, 4: vdac025. PMID: 35402913, PMCID: PMC8989388, DOI: 10.1093/noajnl/vdac025.Peer-Reviewed Original ResearchSafety/tolerabilityNew safety signalsOverall survivalCheckMate 143Median OSSafety signalsGrade 3/4 treatment-related adverse eventsTreatment-related adverse eventsEfficacy of nivolumabImmune checkpoint inhibitionMedian overall survivalPhase 1 cohortFirst-line treatmentPart APrimary endpointSecondary endpointsAdverse eventsCheckpoint inhibitionPatientsI cohortNivolumabTemozolomideRadiotherapyMonthsPart B
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
2014
PHASE II TRIAL OF THE PHOSPHATIDYINOSITOL-3 KINASE (PI3K) INHIBITOR BUPARLISIB (BKM120) IN RECURRENT GLIOBLASTOMA CONDUCTED BY THE IVY FOUNDATION EARLY PHASE CLINICAL TRIALS CONSORTIUM
Wen P, Wen P, Yung W, Mellinghoff I, Ramkissoon S, Alexander B, Rinne M, Colman H, Omuro A, DeAngelis L, Gilbert M, DeGroot J, Cloughesy T, Lee E, Nayak L, S. A, Batchelor T, Chang S, Prados M, Reardon D, Ligon K. PHASE II TRIAL OF THE PHOSPHATIDYINOSITOL-3 KINASE (PI3K) INHIBITOR BUPARLISIB (BKM120) IN RECURRENT GLIOBLASTOMA CONDUCTED BY THE IVY FOUNDATION EARLY PHASE CLINICAL TRIALS CONSORTIUM. Neuro-Oncology 2014, 16: iii47-iii47. PMCID: PMC4144634, DOI: 10.1093/neuonc/nou209.20.Peer-Reviewed Original ResearchPI3K pathwayCohort 2Cohort 1Pan-class I PI3K inhibitorEnzyme-inducing antiepileptic drugsAdequate bone marrowGrade 4 toxicityGrowth of U87K pathwayGrade 3 toxicityPhase II studyPhase II trialRecurrent GBM patientsAdditional eligibility criteriaALT/ASTSingle-agent efficacyPotential therapeutic targetPI3K mutationsReduction of pAKTPI3K inhibitorsEvaluable patientsMedian OSMedian PFSPrior bevacizumabRadiologic progressionMethotrexate re-challenge for recurrent primary central nervous system lymphoma
Pentsova E, DeAngelis LM, Omuro A. Methotrexate re-challenge for recurrent primary central nervous system lymphoma. Journal Of Neuro-Oncology 2014, 117: 161-165. PMID: 24481997, PMCID: PMC5256683, DOI: 10.1007/s11060-014-1370-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntimetabolites, AntineoplasticCentral Nervous System NeoplasmsDisease ProgressionDisease-Free SurvivalFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMaleMethotrexateMiddle AgedNeoplasm Recurrence, LocalPrognosisRetreatmentRetrospective StudiesSalvage TherapyTreatment OutcomeConceptsPrimary CNS lymphomaKarnofsky performance scoreProgression-free survivalInitial diagnosisRecurrent primary central nervous system lymphomaPrimary central nervous system lymphomaMedian Karnofsky performance scoreMedian progression-free survivalCentral nervous system lymphomaObjective response rateNervous system lymphomaMedian OSCNS lymphomaFree survivalRecurrent diseaseSalvage treatmentFirst relapsePartial responsePCNSL patientsPrognostic factorsComplete responseMedian ageSystem lymphomaDisease relapseMedian time
2010
Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide
Kaloshi G, Sierra del Rio M, Ducray F, Psimaras D, Idbaih A, Laigle-Donadey F, Taillibert S, Houillier C, Dehais C, Omuro A, Sanson M, Delattre JY, Hoang-Xuan K. Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide. Journal Of Neuro-Oncology 2010, 100: 439-441. PMID: 20464625, DOI: 10.1007/s11060-010-0197-6.Peer-Reviewed Original ResearchConceptsLow-grade gliomasGrade gliomasProgressive low-grade gliomaTerms of PFSContrast enhancementEfficacy of nitrosoureasBetter PFSMedian PFSMedian OSObjective responseSalvage treatmentUpfront therapyMedian ageBetter prognosisInitial treatmentConventional radiotherapyChromosome 1p/19q codeletionNon-enhancing tumorResponse ratePatientsTemozolomidePure oligodendrogliomasPFSGliomasDisappointing results