2023
Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma
Fanucci K, Pilat M, Shyr D, Shyr Y, Boerner S, Li J, Durecki D, Drappatz J, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma. Cancer Research Communications 2023, 3: 192-201. PMID: 36968138, PMCID: PMC10035510, DOI: 10.1158/2767-9764.crc-22-0436.Peer-Reviewed Original ResearchConceptsProgression-free survivalMedian progression-free survivalProlonged stable diseaseStable diseasePhase II trialGrade 4 tumorsII trialOlaparib monotherapyGrade 2Multicenter phase 2 trialSingle-arm phase II trialWorld Health Organization classificationMedian overall survivalNeuro-Oncology criteriaPhase 2 trialOverall response rateFuture patient stratificationMutant gliomasPARP inhibitor olaparibEvaluable patientsPrimary endpointOverall survivalProgressive diseaseSelect patientsClinical benefit
2022
Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma.
Fanucci K, Pilat M, Shah R, Boerner S, Li J, Durecki D, Drappatz J, Collichio F, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Bao X, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter phase 2 trial of the PARP inhibitor (PARPi) olaparib in recurrent IDH1 and IDH2-mutant contrast-enhancing glioma. Journal Of Clinical Oncology 2022, 40: 2035-2035. DOI: 10.1200/jco.2022.40.16_suppl.2035.Peer-Reviewed Original ResearchProgression-free survivalMedian progression-free survivalStable diseaseDuration of responseOverall response ratePARP inhibitorsOverall survivalStandard therapyOlaparib monotherapyMulticenter phase 2 trialCDKN2A deletionClinical predictive markersGrade 3 lymphopeniaProlonged stable diseasePhase 2 trialGrade 4 tumorsFuture patient stratificationRecent preclinical studiesHigh-grade gliomasNovel drug combinationsContrast-enhancing gliomasEligible ptsEvaluable ptsRecent histologyPrimary endpoint
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 evaluationPhase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL).
Tun H, Johnston P, Grommes C, Reeder C, Omuro A, Menke D, Copland J, DeAngelis L, Witzig T. Phase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL). Journal Of Clinical Oncology 2017, 35: 7516-7516. DOI: 10.1200/jco.2017.35.15_suppl.7516.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaOverall response rateRefractory primary central nervous system lymphomaPhase I clinical trialPrimary vitreoretinal lymphomaMTD cohortStable diseaseClinical trialsCentral nervous system lymphomaTherapeutic activityDiffuse large B-cell lymphomaLarge B-cell lymphomaDose level 3Grade 3/4 toxicitiesNovel immunomodulatory agentsNervous system lymphomaCycles of treatmentDose escalation levelsCSF/blood ratioB-cell lymphomaExcellent CNS penetrationPO weeklyPomalidomide treatmentPseudo progressionCNS lymphoma
2015
Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma
Wen PY, Omuro A, Ahluwalia MS, Fathallah-Shaykh HM, Mohile N, Lager JJ, Laird AD, Tang J, Jiang J, Egile C, Cloughesy TF. Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma. Neuro-Oncology 2015, 17: 1275-1283. PMID: 26019185, PMCID: PMC4588757, DOI: 10.1093/neuonc/nov083.Peer-Reviewed Original ResearchConceptsHigh-grade gliomasAdverse eventsRadiation therapySkin biopsiesPhase I dose-escalation studyTreatment-related adverse eventsI dose-escalation studyPI3K/mTOR pathway inhibitionTreatment-related gradeDose-escalation studyDose-escalation designFavorable safety profileMTOR pathway inhibitionEvaluable patientsStable diseasePartial responsePharmacodynamic effectsPlatelet countRapamycin inhibitorsSafety profilePreliminary efficacyTumor responsePlasma pharmacokineticsVoxtalisibPatients
2013
A phase I study of carboxyamidotriazole orotate (CTO) in of advanced solid tumors.
Sandler A, Taylor M, Urba W, Omuro A, Anderson B, Hansen D, Fisher B, Claeys A, Greathouse A, McLean S, Karmali R. A phase I study of carboxyamidotriazole orotate (CTO) in of advanced solid tumors. Journal Of Clinical Oncology 2013, 31: 2518-2518. DOI: 10.1200/jco.2013.31.15_suppl.2518.Peer-Reviewed Original ResearchAdvanced solid tumorsCell lung cancerStable diseaseLung cancerSolid tumorsSquamous cell lung cancerSmall cell lung cancerAdequate organ functionGrade 3 fatigueCreatine kinase elevationSquamous cell carcinomaColon tumor xenograftsAnti-tumor effectsAnti-invasive propertiesPharmacokinetic samplingAdverse eventsQTc prolongationCell carcinomaTumor responseEGFR mutationsPIK3CA mutationsMalignant gliomasLung adenocarcinomaTumor assessmentCT scan
2012
Atypical and anaplastic meningiomas treated with bevacizumab
Nayak L, Iwamoto FM, Rudnick JD, Norden AD, Lee EQ, Drappatz J, Omuro A, Kaley TJ. Atypical and anaplastic meningiomas treated with bevacizumab. Journal Of Neuro-Oncology 2012, 109: 187-193. PMID: 22544653, DOI: 10.1007/s11060-012-0886-4.Peer-Reviewed Original ResearchConceptsProgression-free survivalVascular endothelial growth factor receptorAnaplastic meningiomasRadiographic responseMedian progression-free survivalBest radiographic responseEfficacy of bevacizumabMonths PFS rateEndothelial growth factor receptorKaplan-Meier statisticsActivity of bevacizumabEffective chemotherapeutic optionsAnti-angiogenic agentsTumor blood volumeMR perfusion studiesGrowth factor receptorPFS ratesStable diseaseBevacizumab therapyOverall survivalRANO criteriaRetrospective reviewSurgical optionsProspective studyAggressive tumors
2011
A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression
Mason WP, Belanger K, Nicholas G, Vallières I, Mathieu D, Kavan P, Desjardins A, Omuro A, Reymond D. A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression. Journal Of Neuro-Oncology 2011, 107: 343-349. PMID: 22048878, DOI: 10.1007/s11060-011-0747-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBrain NeoplasmsChromatography, LiquidDibenzazepinesErbB ReceptorsFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticGlioblastomaHumansInfusions, IntraventricularKaplan-Meier EstimateMagnetic Resonance ImagingMaleMiddle AgedPTEN PhosphohydrolaseTandem Mass SpectrometryConceptsPharmacokinetic evaluationProgressive glioblastomaFirst progressionM2/dayPhase II studyMR scansPhase II trialContinuous intravenous administrationBlood-brain barrierLack of efficacyPeripheral benzodiazepine receptorEvaluable patientsStable diseaseII trialRadiographic progressionAdverse eventsII studyRecurrent glioblastomaDisease progressionDrug levelsIntravenous administrationBiomarker assessmentPatientsAnimal modelsBenzodiazepine receptors
2010
Up-front temozolomide in elderly patients with anaplastic oligodendroglioma and oligoastrocytoma
Ducray F, Sierra del Rio M, Carpentier C, Psimaras D, Idbaih A, Dehais C, Kaloshi G, Mokhtari K, Taillibert S, Laigle-Donadey F, Omuro A, Sanson M, Delattre JY, Hoang-Xuan K. Up-front temozolomide in elderly patients with anaplastic oligodendroglioma and oligoastrocytoma. Journal Of Neuro-Oncology 2010, 101: 457-462. PMID: 20556480, DOI: 10.1007/s11060-010-0264-z.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic Agents, AlkylatingBrain NeoplasmsDacarbazineDNA MethylationDNA Modification MethylasesDNA Repair EnzymesDNA, NeoplasmFemaleFollow-Up StudiesHumansMaleOligodendrogliomaPolymerase Chain ReactionPromoter Regions, GeneticRetrospective StudiesSurvival RateTemozolomideTreatment OutcomeTumor Suppressor ProteinsConceptsProgression-free survivalAnaplastic oligodendroglial tumorsElderly patientsOverall survivalFront chemotherapyPartial responseMedian progression-free survivalLonger progression-free survivalInitial radiation therapyLonger overall survivalDuration of responseRate of respondersO6-methylguanine-DNA methyltransferase (MGMT) promoter methylationMethyltransferase promoter methylationEvaluable patientsStable diseaseConsecutive patientsConventional dosesRetrospective studyOptimal treatmentAnaplastic oligodendrogliomaRadiation therapyPatientsOligodendroglial tumorsTumor progression
2009
Patterns of care and outcomes in patients with intracranial hemangiopericytomas: The Memorial Sloan-Kettering Cancer Center (MSKCC) experience
Dankwah-Quansah M, Gutin P, Bilsky M, Huse J, Rosenblum M, Abrey L, DeAngelis L, Omuro A. Patterns of care and outcomes in patients with intracranial hemangiopericytomas: The Memorial Sloan-Kettering Cancer Center (MSKCC) experience. Journal Of Clinical Oncology 2009, 27: e13011-e13011. DOI: 10.1200/jco.2009.27.15_suppl.e13011.Peer-Reviewed Original ResearchIntracranial hemangiopericytomaStable diseaseDisease courseMemorial Sloan-Kettering Cancer Center experienceMedian progression-free survivalRare primary brain tumorsTargeted therapy eraMedian overall survivalProgression-free survivalCancer Center experienceOptimal clinical managementPatterns of carePrimary brain tumorsEfficacy of chemotherapyAdditional radiotherapyMedian KPSTherapy eraAdjuvant radiotherapySalvage treatmentCytotoxic chemotherapyOverall survivalSurgical resectionCenter experienceMedian ageRetrospective review
2007
A phase II trial of vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases
Iwamoto FM, Omuro AM, Raizer JJ, Nolan CP, Hormigo A, Lassman AB, Gavrilovic IT, Abrey LE. A phase II trial of vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases. Journal Of Neuro-Oncology 2007, 87: 85-90. PMID: 17987262, DOI: 10.1007/s11060-007-9491-3.Peer-Reviewed Original ResearchConceptsKarnofsky Performance ScaleProgressive brain metastasesPhase II trialBrain metastasesII trialResponse rateMedian Karnofsky performance scaleWhole-brain radiation therapyAdequate organ functionBrain metastasis resectionObjective radiographic responseRadiographic response rateSingle-agent temozolomideGrade 3/4 toxicitiesRecurrent brain metastasesPopulation of patientsPrimary tumor siteYears of agePrior therapyStable diseaseVinorelbine 25Metastasis resectionPrimary endpointMethods PatientsOverall survivalTemozolomide for low-grade gliomas
Kaloshi G, Benouaich-Amiel A, Diakite F, Taillibert S, Lejeune J, Laigle-Donadey F, Renard M, Iraqi W, Idbaih A, Paris S, Capelle L, Duffau H, Cornu P, Simon J, Mokhtari K, Polivka M, Omuro A, Carpentier A, Sanson M, Delattre J, Hoang-Xuan K. Temozolomide for low-grade gliomas. Neurology 2007, 68: 1831-1836. PMID: 17515545, DOI: 10.1212/01.wnl.0000262034.26310.a2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, AlkylatingBrain NeoplasmsChromosome DeletionChromosomes, Human, Pair 1Chromosomes, Human, Pair 19DacarbazineDNA Mutational AnalysisDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticGenetic TestingGenotypeGliomaHumansLoss of HeterozygosityMaleMiddle AgedNeoplasm Recurrence, LocalRetrospective StudiesSurvival RateTemozolomideTreatment OutcomeConceptsProgression-free survivalLow-grade gliomasProgressive low-grade gliomaObjective responseMedian progression-free survivalLonger progression-free survivalSingle-center observational studyCenter observational studyMaximum tumor responseStable diseaseProgressive diseaseAdult patientsConsecutive patientsOverall survivalMedian timeTMZ cyclesTemozolomide chemotherapyCentral reviewTumor responseFavorable outcomeMedian numberObservational studyPatientsPredictive impactConventional schedule
2005
Salvage temozolomide for prior temozolomide responders
Franceschi E, Omuro AM, Lassman AB, Demopoulos A, Nolan C, Abrey LE. Salvage temozolomide for prior temozolomide responders. Cancer 2005, 104: 2473-2476. PMID: 16270316, DOI: 10.1002/cncr.21564.Peer-Reviewed Original ResearchConceptsDisease recurrenceRecurrent/progressive gliomaInitial disease recurrencePotential hematologic complicationsSubsequent salvage therapyFirst-line therapyProgression-free survivalTime of diagnosisLow-grade oligodendrogliomasWarrants further investigationSalvage therapyStable diseaseHematologic complicationsObjective responseRadiographic responseMedian ageRetrospective reviewDisease progressionTMZ treatmentAnaplastic astrocytomaPatientsProgressive gliomasRecurrenceTemozolomideSame agents