2024
Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations
Yasin F, Sokol E, Vasan N, Pavlick D, Huang R, Pelletier M, Levy M, Pusztai L, Lacy J, Zhang J, Ross J, Cecchini M. Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations. The Oncologist 2024, oyae259. PMID: 39401325, DOI: 10.1093/oncolo/oyae259.Peer-Reviewed Original ResearchAdvanced colorectal cancerPIK3CA mutationsColorectal cancerPI3K inhibitionPI3K inhibitorsBurden of colorectal cancerActivating mutationsResponse to PI3K inhibitionSensitive to PI3K inhibition.Foundation Medicine databaseMetastatic colorectal cancerClinically relevant mutationsMicrosatellite instability-highPI3K signalingTumor DNAPIK3CA variantsClinical carePIK3CA oncogeneClinical variablesE545KGenomic profilingPIK3CAE542KMedicine DatabasePatientsARC-9: A randomized study to evaluate etrumadenant based treatment combinations in previously treated metastatic colorectal cancer (mCRC).
Wainberg Z, Han S, Lee S, Lee K, Kopetz S, Mizrahi J, Hong Y, Ghiringhelli F, Italiano A, Tougeron D, Beagle B, Boakye M, Zhao T, Rhee J, Nuyten D, Cecchini M. ARC-9: A randomized study to evaluate etrumadenant based treatment combinations in previously treated metastatic colorectal cancer (mCRC). Journal Of Clinical Oncology 2024, 42: 3508-3508. DOI: 10.1200/jco.2024.42.16_suppl.3508.Peer-Reviewed Original ResearchProgression-free survivalMetastatic colorectal cancerOverall survivalCohort BActivation of effector T cellsManagement of metastatic colorectal cancerAnti-PD-1 antibodyTreat metastatic colorectal cancerTreated with 5-FURandomized phase II clinical trialIrinotecan-containing regimensPhase Ib/II trialPhase II clinical trialEffector T cellsAdenosine receptor blockadeCohort of patientsII clinical trialsIrinotecan regimensMFOLFOX-6OS improvementReceptor blockadePrimary endpointProspective trialsReceptor antagonistSecondary endpoints
2023
Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Cecchini M, Zhang J, Wei W, Sklar J, Lacy J, Zhong M, Kong Y, Zhao H, DiPalermo J, Devine L, Stein S, Kortmansky J, Johung K, Bindra R, LoRusso P, Schalper K. Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer. Cancer Research Communications 2023, 3: 1132-1139. PMID: 37387791, PMCID: PMC10305782, DOI: 10.1158/2767-9764.crc-23-0045.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingMGMT protein expressionColorectal cancerStable diseaseQuantitative immunofluorescenceT cellsProtein expressionPromoter hypermethylationLow MGMT protein expressionPARP inhibitorsRadiographic tumor regressionMetastatic colorectal cancerAdvanced colorectal cancerPretreatment tumor biopsiesEffector T cellsTumor-infiltrating lymphocytesMGMT proteinDNA repair biomarkersBaseline CD8Eligible patientsIncreased CD8Methylguanine-DNA methyltransferaseObjective responseProgressive diseaseImmune markers
2022
Hybrid-control arm construction using historical trial data for an early-phase, randomized controlled trial in metastatic colorectal cancer
Li C, Ferro A, Mhatre SK, Lu D, Lawrance M, Li X, Li S, Allen S, Desai J, Fakih M, Cecchini M, Pedersen KS, Kim TY, Reyes-Rivera I, Segal NH, Lenain C. Hybrid-control arm construction using historical trial data for an early-phase, randomized controlled trial in metastatic colorectal cancer. Communications Medicine 2022, 2: 90. PMID: 35856081, PMCID: PMC9287310, DOI: 10.1038/s43856-022-00155-y.Peer-Reviewed Original ResearchMetastatic colorectal cancerExperimental armColorectal cancerMetastatic colorectal cancer (mCRC) trialsMetastatic colorectal cancer patientsPhase Ib/IITrial dataHistorical trial dataColorectal cancer trialsDisease control rateObjective response ratePhase 3 trialProgression-free survivalColorectal cancer patientsStandardized mortality ratioEarly phase trialsEarly phase clinical developmentLogistic regression modelsMultiple experimental armsPrimary endpointOverall survivalPrior linesEfficacy signalsSafety profileCombination therapy
2021
Abstract CT129: ARC-3: Updated results of etrumadenant (AB928) + modified FOLFOX-6 (mFOLFOX-6) in metastatic colorectal cancer (mCRC) patients
Cecchini M, Quah C, Liu S, Woloski R, Udyavar A, Giannakis M. Abstract CT129: ARC-3: Updated results of etrumadenant (AB928) + modified FOLFOX-6 (mFOLFOX-6) in metastatic colorectal cancer (mCRC) patients. Cancer Research 2021, 81: ct129-ct129. DOI: 10.1158/1538-7445.am2021-ct129.Peer-Reviewed Original ResearchModified FOLFOX-6Metastatic colorectal cancerFOLFOX-6American Association for Cancer Research annual meetingsColorectal cancerAnti-tumor immune responseAssociated with disease controlDying cancer cellsMCRC ptsAdenosine receptor blockadeOpen-label studyRelease of ATPAntagonists of A2ARMedian PFSPretreated ptsReceptor blockadeEligible ptsOrally onceExtracellular adenosineA2B receptorsImmune cellsChemotherapeutic agentsTherapeutic efficacyClinical activityImmune responseARC-9: Phase Ib/II study to evaluate etrumadenant (AB928)-based treatment combinations in patients with metastatic colorectal cancer (mCRC).
Cecchini M, Krishnan K, Giafis N, Scott J, Quah C, Bendell J. ARC-9: Phase Ib/II study to evaluate etrumadenant (AB928)-based treatment combinations in patients with metastatic colorectal cancer (mCRC). Journal Of Clinical Oncology 2021, 39: tps150-tps150. DOI: 10.1200/jco.2021.39.3_suppl.tps150.Peer-Reviewed Original ResearchMetastatic colorectal cancerStandard-of-careStandard-of-care armMFOLFOX-6Cohort BCohort AActivation of effector T cellsModified 5-fluorouracilTreated with FOLFOXDying cancer cellsDose-escalation studyEffector T cellsPhase Ib/II studyAdenosine receptor blockadeAdenosine receptor antagonistPhase 1b/2Escalation studyCurative intentReceptor blockadeOpen-labelImmunosuppressive adenosineCombination therapyPrimary endpointReceptor antagonistCohort C
2020
A phase 1b expansion study of TAS‐102 with oxaliplatin for refractory metastatic colorectal cancer
Cecchini M, Kortmansky JS, Cui C, Wei W, Thumar JR, Uboha NV, Hafez N, Lacy J, Fischbach NA, Sabbath KD, Gomez CM, Sporn JR, Stein S, Hochster HS. A phase 1b expansion study of TAS‐102 with oxaliplatin for refractory metastatic colorectal cancer. Cancer 2020, 127: 1417-1424. PMID: 33351187, PMCID: PMC8085021, DOI: 10.1002/cncr.33379.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsColorectal NeoplasmsDrug Administration ScheduleDrug CombinationsDrug Resistance, NeoplasmFemaleFluorouracilHumansIrinotecanLeucovorinMaleMiddle AgedOrganoplatinum CompoundsOxaliplatinProgression-Free SurvivalPyrrolidinesResponse Evaluation Criteria in Solid TumorsThymineTrifluridineConceptsMetastatic colorectal cancerOverall response rateRefractory metastatic colorectal cancerProgression-free survivalTAS-102Colorectal cancerDay 1Primary endpointOverall survivalDose escalationDay 5Median progression-free survivalPhase 1b studyMedian overall survivalResponse Evaluation CriteriaTreat populationDose expansionPartial responseStandard dosesUnexpected side effectsStudy treatmentTumor shrinkageUnexpected toxicitiesSide effectsNovel antimetabolite338 Emerging insights on the association of tumor molecular phenotype with clinical benefit in metastatic colorectal cancer (mCRC) subjects treated with AB928 + modified FOLFOX-6 (mFOLFOX-6)
Udyavar A, Cecchini M, DiRenzo D, Cho S, Seitz L, Zhang K, Young S, Anderson A, Gerrick K, Walters M, Gilbert H, Gardner O, Quah C, Jaen J, Grossman W. 338 Emerging insights on the association of tumor molecular phenotype with clinical benefit in metastatic colorectal cancer (mCRC) subjects treated with AB928 + modified FOLFOX-6 (mFOLFOX-6). Journal For ImmunoTherapy Of Cancer 2020, 8: a206-a207. DOI: 10.1136/jitc-2020-sitc2020.0338.Peer-Reviewed Original ResearchModified FOLFOX-6Metastatic colorectal cancerFOLFOX-6Clinical benefitColorectal cancerTumor molecular phenotypeMolecular phenotypesAbstract LB-387: Efficacy and safety of AB928 plus modified FOLFOX-6 (mFOLFOX-6) in participants with metastatic colorectal cancer (mCRC): Initial results at the recommended dose for expansion (ARC-3)
Cecchini M, Modiano M, Braiteh F, Gardner O, Gilbert H, DiRenzo D, Seitz L, Walters M, Yin F, Woloski R, Paoloni M, Chung K. Abstract LB-387: Efficacy and safety of AB928 plus modified FOLFOX-6 (mFOLFOX-6) in participants with metastatic colorectal cancer (mCRC): Initial results at the recommended dose for expansion (ARC-3). Cancer Research 2020, 80: lb-387-lb-387. DOI: 10.1158/1538-7445.am2020-lb-387.Peer-Reviewed Original ResearchModified FOLFOX-6Metastatic colorectal cancerAdverse eventsPhase 1bFOLFOX-6Stable diseaseColorectal cancerAnti-tumor immune responseECOG performance status 0Recommended doseAssociated with disease controlExploratory biomarker analysesTumor shrinkage >Disease control rateDying cancer cellsGrade 3 AEsPerformance status 0Dose-escalation studyAdenosine receptor blockadeOpen-label studyAmerican Association for Cancer ResearchAdenosine receptor antagonistRelease of ATPNext gene sequencingAdenosine axis
2019
A phase I study of TAS-102 in combination with oxaliplatin (TAS-OX) for refractory metastatic colorectal cancer (mCRC).
Cecchini M, Kortmansky J, Lacy J, Fischbach N, Thumar J, Sabbath K, Gomez C, Sporn J, Stein S, Hochster H. A phase I study of TAS-102 in combination with oxaliplatin (TAS-OX) for refractory metastatic colorectal cancer (mCRC). Journal Of Clinical Oncology 2019, 37: 630-630. DOI: 10.1200/jco.2019.37.4_suppl.630.Peer-Reviewed Original ResearchDisease control rateMetastatic colorectal cancerTAS-102Progressive diseaseDay 1Thymidine phosphorylase inhibitorRefractory metastatic colorectal cancerDose-escalating studyECOG PS 0Phase II doseEfficacy of oxaliplatinUsual laboratory parametersEligible patientsEvaluable patientsMeasurable diseaseUnexpected AEsStarting doseTreatment discontinuationPS 0Improved survivalLaboratory parametersOral combinationColorectal cancerPatient populationControl rate
2016
Chemotherapy induced neutropenia at 1-month mark is a predictor of overall survival in patients receiving TAS-102 for refractory metastatic colorectal cancer: a cohort study
Kasi PM, Kotani D, Cecchini M, Shitara K, Ohtsu A, Ramanathan RK, Hochster HS, Grothey A, Yoshino T. Chemotherapy induced neutropenia at 1-month mark is a predictor of overall survival in patients receiving TAS-102 for refractory metastatic colorectal cancer: a cohort study. BMC Cancer 2016, 16: 467. PMID: 27412464, PMCID: PMC4944251, DOI: 10.1186/s12885-016-2491-y.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgedAntineoplastic AgentsChemotherapy-Induced Febrile NeutropeniaClinical Trials, Phase III as TopicCohort StudiesColorectal NeoplasmsDisease-Free SurvivalDose-Response Relationship, DrugDrug CombinationsDrug Resistance, NeoplasmFemaleHumansJapanKaplan-Meier EstimateMaleMiddle AgedPrognosisPyrrolidinesThymineTrifluridineUnited StatesUracilConceptsMetastatic colorectal cancerProgression-free survivalOverall survivalCohort studyGrade 2Median progression-free survivalRefractory metastatic colorectal cancerLonger progression-free survivalNeutrophil count decreaseCommon Terminology CriteriaBetter overall survivalKaplan-Meier methodChemotherapy-induced neutropeniaLog-rank testTerminology CriteriaAdverse eventsClinical characteristicsPatient demographicsStandard therapyTAS-102Colorectal cancerOutcome dataPatientsCount decreaseRegulatory approval