2024
A Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer
Jia J, Moyer A, Lowe M, Bolch E, Kortmansky J, Cho M, Lenz H, Kalyan A, Niedzwiecki D, Strickler J. A Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer. Journal Of Gastrointestinal Cancer 2024, 56: 29. PMID: 39652198, DOI: 10.1007/s12029-024-01156-x.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsMetastatic colorectal cancerPhase 2 studyEpidermal growth factor receptorAnti-tumor activityStable diseaseProgressive diseaseChemotherapy refractory metastatic colorectal cancerOral small-molecule tyrosine kinase inhibitorColorectal cancerResistance to epidermal growth factor receptorSmall molecule tyrosine kinase inhibitorsRefractory metastatic colorectal cancerBest overall responseRAS wild-typeAdvanced solid tumorsBiomarker-selected patientsTyrosine kinase inhibitorsWild-typeGrowth factor receptorResultsFive patientsPrimary endpointSecondary endpointsSolid tumorsSavolitinibMolecular 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, 29: 1059-1067. PMID: 39401325, PMCID: PMC11630746, 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 DatabasePatientsTislelizumab plus cetuximab and irinotecan in refractory microsatellite stable and RAS wild-type metastatic colorectal cancer: a single-arm phase 2 study
Xu X, Ai L, Hu K, Liang L, Lv M, Wang Y, Cui Y, Li W, Li Q, Yu S, Feng Y, Liu Q, Yang Y, Zhang J, Xu F, Yu Y, Liu T. Tislelizumab plus cetuximab and irinotecan in refractory microsatellite stable and RAS wild-type metastatic colorectal cancer: a single-arm phase 2 study. Nature Communications 2024, 15: 7255. PMID: 39179622, PMCID: PMC11343749, DOI: 10.1038/s41467-024-51536-x.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerVariant allele frequencyPhase 2 studyEpidermal growth factor receptorAdverse eventsRAS wild-type metastatic colorectal cancerRAS wt metastatic colorectal cancerSingle-arm phase 2 studyWild-type metastatic colorectal cancerColorectal cancerTreatment-related adverse eventsAnti-PD-1Disease control rateProgression-free survivalRAS wild-typeTumor immune responseCombined treatment regimenWild-typeGrowth factor receptorIrinotecan combinationOverall survivalAnti-EGFRPrimary endpointTumor DNASingle-armEncorafenib and cetuximab versus irinotecan/cetuximab or FOLFIRI/cetuximab in Chinese patients with BRAF V600E mutant metastatic colorectal cancer: The NAUTICAL CRC study.
Wang X, Deng Y, Zhang Y, Liu T, Yuan X, Yang J, Zhang T, Zang A, Liu Y, Huang L, Ye F, Zong H, Ba Y, Klauck I, Vedovato J, Groc M, Guo A, Shen L. Encorafenib and cetuximab versus irinotecan/cetuximab or FOLFIRI/cetuximab in Chinese patients with BRAF V600E mutant metastatic colorectal cancer: The NAUTICAL CRC study. Journal Of Clinical Oncology 2024, 42: lba3559-lba3559. DOI: 10.1200/jco.2024.42.17_suppl.lba3559.Peer-Reviewed Original ResearchMutant metastatic colorectal cancerTreatment-emergent adverse eventsMetastatic colorectal cancerBRAF V600E mutationChinese patientsControl armMetastatic treatmentV600E mutationGrade 3BRAF V600E-mutated mCRCFrequent treatment-emergent adverse eventsColorectal cancerTreatment-related grade 3CRC studyBaseline ECOG performance statusCombination of encorafenibSafety lead-inEmergent adverse eventsData cut-offMedian patient ageECOG performance statusPrimary cancer siteConfirmed ORRMedian OSMedian PFSA phase II trial of UGT1A1 genotype-guided FOLFIRI plus bevacizumab as first-line therapy for advanced, unresectable colorectal cancer
Sanoff H, Deal A, Patel J, Sorah J, Gaddy J, O’Neil B, Turk A, Irvin W, Boles J, Lee M, McRee A, Wardell A, Weck K, Basch E, Wood W, Innocenti F. A phase II trial of UGT1A1 genotype-guided FOLFIRI plus bevacizumab as first-line therapy for advanced, unresectable colorectal cancer. The Oncologist 2024, 29: 786-793. PMID: 38837045, PMCID: PMC11379652, DOI: 10.1093/oncolo/oyae122.Peer-Reviewed Original ResearchProgression-free survivalMetastatic colorectal cancerOverall survivalIrinotecan doseColorectal cancerMedian progression-free survivalMetastatic colorectal cancer patientsEstimates of overall survivalFirst-line settingUnresectable colorectal cancerRates of neutropeniaFirst-line therapyPhase II trialPatient-reported adverse eventsRate of diarrheaG3/4 toxicitiesUGT1A1 genotypeIrinotecan metabolismFirst-linePrimary endpointSecondary endpointsAdverse eventsFOLFIRIHistorical controlsNon-genotypeColon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.
Benson A, Venook A, Adam M, Chang G, Chen Y, Ciombor K, Cohen S, Cooper H, Deming D, Garrido-Laguna I, Grem J, Haste P, Hecht J, Hoffe S, Hunt S, Hussan H, Johung K, Joseph N, Kirilcuk N, Krishnamurthi S, Malla M, Maratt J, Messersmith W, Meyerhardt J, Miller E, Mulcahy M, Nurkin S, Overman M, Parikh A, Patel H, Pedersen K, Saltz L, Schneider C, Shibata D, Shogan B, Skibber J, Sofocleous C, Tavakkoli A, Willett C, Wu C, Gurski L, Snedeker J, Jones F. Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology. Journal Of The National Comprehensive Cancer Network 2024, 22 PMID: 38862008, DOI: 10.6004/jnccn.2024.0029.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerColorectal cancerNCCN Clinical Practice GuidelinesSystemic therapy optionsGoal of therapyClinical practice guidelinesNCCN GuidelinesToxicity profileTherapy optionsColon cancerMutation profilesActive drugCancer deathDiagnosed cancerCancerConstituent drugsTherapyPractice guidelinesNCCNDrugTumorColorectalGuidelinesUnited StatesOncologyARC-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 endpointsA phase 1b study of NC410 in combination with pembrolizumab in immune checkpoint inhibitor (ICI) naïve, and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC) and ovarian cancer.
Christenson E, Mahadevan D, Kazmi S, Manda S, Sohal D, Hutson T, Fu S, Martz A, Kordahi S, Barbu E, Flies D, Langermann S, Chisamore M, Gutierrez M, Matrana M, Spira A, Wadlow R, Guha U, Myint H, Le D. A phase 1b study of NC410 in combination with pembrolizumab in immune checkpoint inhibitor (ICI) naïve, and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC) and ovarian cancer. Journal Of Clinical Oncology 2024, 42: 2538-2538. DOI: 10.1200/jco.2024.42.16_suppl.2538.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsImmune cell infiltrationOvarian cancerColorectal cancerICI therapyCell infiltrationAdvanced metastatic colorectal cancerPromote immune cell infiltrationResistance to ICI therapyEffector memory T cellsPeripheral blood immunophenotypingPhase 1b/2 studyDose of pembrolizumabData cut-offMetastatic colorectal cancerMetastatic solid tumorsMemory T cellsColorectal cancer subjectsImmune cell functionHuman IgG1 Fc domainAnti-tumor activityTumor extracellular matrixModified toxicity probability intervalExtracellular matrixCheckpoint inhibitorsResults from phase 1a/1b analyses of TTX-080, a first in class HLA-G antagonist, in combination with cetuximab in patients (pts) with metastatic colorectal cancer and head and neck squamous cell carcinoma.
Ulahannan S, Marron T, Park H, Kaczmar J, Stephenson R, Lakhani N, Durm G, Grewal J, El-Khoueiry A, Luke J, Beers C, Murugappan S, LoRusso P, Adkins D, Hecht J. Results from phase 1a/1b analyses of TTX-080, a first in class HLA-G antagonist, in combination with cetuximab in patients (pts) with metastatic colorectal cancer and head and neck squamous cell carcinoma. Journal Of Clinical Oncology 2024, 42: 2524-2524. DOI: 10.1200/jco.2024.42.16_suppl.2524.Peer-Reviewed Original ResearchHead and neck squamous cell carcinomaMetastatic colorectal cancerNeck squamous cell carcinomaSquamous cell carcinomaPreliminary efficacy dataCell carcinomaColorectal cancerEfficacy dataSolid tumor cohortTreatment-related AEsImmune cell changesAnti-tumor activityStandard of careRandomized controlled studyDose escalationEscalating dosesHLA-G.Peripheral bloodTumor cohortsSolid tumorsDecreased appetiteAST increaseBlood samplesCell changesQ3WPembrolizumab Plus Binimetinib With or Without Chemotherapy for MSS/pMMR Metastatic Colorectal Cancer: Outcomes From KEYNOTE-651 Cohorts A, C, and E
Chen E, Kavan P, Tehfe M, Kortmansky J, Sawyer M, Chiorean E, Lieu C, Polite B, Wong L, Fakih M, Spencer K, Chaves J, Li C, Leconte P, Adelberg D, Kim R. Pembrolizumab Plus Binimetinib With or Without Chemotherapy for MSS/pMMR Metastatic Colorectal Cancer: Outcomes From KEYNOTE-651 Cohorts A, C, and E. Clinical Colorectal Cancer 2024, 23: 183-193. PMID: 38653648, DOI: 10.1016/j.clcc.2024.03.002.Peer-Reviewed Original ResearchObjective response rateMetastatic colorectal cancerCohort ACohort CCohort EDose escalationInvestigator-assessed objective response rateColorectal cancerResponse rateModified toxicity probability interval designDose reductionSafety findingsPrimary endpointPembrolizumabBinimetinibLeucovorinE. CONCLUSIONSChemotherapyPatientsCohortIrinotecanOxaliplatinCancerInterval designWeeksPembrolizumab Plus mFOLFOX7 or FOLFIRI for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer: KEYNOTE-651 Cohorts B and D
Kim R, Tehfe M, Kavan P, Chaves J, Kortmansky J, Chen E, Lieu C, Wong L, Fakih M, Spencer K, Zhao Q, Predoiu R, Li C, Leconte P, Adelberg D, Chiorean E. Pembrolizumab Plus mFOLFOX7 or FOLFIRI for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer: KEYNOTE-651 Cohorts B and D. Clinical Colorectal Cancer 2024, 23: 118-127.e6. PMID: 38762348, DOI: 10.1016/j.clcc.2024.03.001.Peer-Reviewed Original ResearchMetastatic colorectal cancerObjective response rateCohort BCohort DAdverse eventsColorectal cancerT-cell-inflamed gene expression profileInvestigator-assessed objective response ratePD-L1 combined positive scoreTreatment-related adverse eventsResponse rateCombined positive scoreDose-limiting toxicityMedian follow-upTumor mutational burdenDecreased neutrophil countPrimary end pointMismatch repair-proficientStandard of careBiomarker analysisMethods PatientsRECIST v1.1PD-L1HER2 expressionMutational burdenEfficacy and Safety of Trifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors: A Systematic Review
Shitara K, Falcone A, Fakih M, George B, Sundar R, Ranjan S, Van Cutsem E. Efficacy and Safety of Trifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors: A Systematic Review. The Oncologist 2024, 29: e601-e615. PMID: 38366864, PMCID: PMC11067808, DOI: 10.1093/oncolo/oyae007.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerRefractory metastatic colorectal cancerAdverse eventsDiscontinuation rate due to adverse eventsColorectal cancerChemorefractory metastatic colorectal cancerSafety outcomesMedian overall survivalSafety of FTD/TPIProgression-free survivalAdvanced solid tumorsAssociated with improved outcomesEarly-phase studiesSystematic reviewOverall survivalFTD/TPIRetrospective studySolid tumorsBevacizumabClinical efficacyTargeted agentsTumor typesAntineoplastic agentsAdvanced cancerImprove outcomesFruquintinib plus paclitaxel versus paclitaxel as second-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma (FRUTIGA): A randomized, multicenter, double-blind, placebo-controlled, phase 3 study.
Xu R, Wang F, Shen L, Guo W, Liu T, Li J, Qin S, Bai Y, Chen Z, Wang J, Pan Y, Shu Y, Zhao F, Cheng Y, Ye F, Gu K, Zhang T, Pan H, Zhong H, Su W. Fruquintinib plus paclitaxel versus paclitaxel as second-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma (FRUTIGA): A randomized, multicenter, double-blind, placebo-controlled, phase 3 study. Journal Of Clinical Oncology 2024, 42: 438780-438780. DOI: 10.1200/jco.2024.42.36_suppl.438780.Peer-Reviewed Original ResearchPhase 3 studyAntitumor therapyMedian OSDouble-blindPrimary endpointInhibitor of VEGFR-1Dose of study drugSecond-line treatment optionDual primary endpointsPlacebo (PBO)-controlledFirst-line chemotherapyGastroesophageal junction adenocarcinomaMetastatic colorectal cancerSecond-line therapyLymph node metastasisTreatment of paclitaxelStatistical significanceCox proportional hazards modelsPost hoc analysisOral inhibitorJunction adenocarcinomaEligible ptsPlacebo-controlledStudy drugStatistically significant improvementUtility of Circulating Tumor DNA Assessment in Characterizing Recurrence Sites after Optimal Resection for Metastatic Colorectal Cancer.
Bansal V, Belmont E, Godley F, Dhiman A, Witmer H, Li S, Liao A, Eng O, Turaga K, Shergill A. Utility of Circulating Tumor DNA Assessment in Characterizing Recurrence Sites after Optimal Resection for Metastatic Colorectal Cancer. Journal Of The American College Of Surgeons 2024, 238: 1013-1020. PMID: 38299640, DOI: 10.1097/xcs.0000000000001028.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerRecurrence siteOptimal resectionCtDNA detectionDistant recurrenceColorectal cancerClinical diagnosis of recurrenceDiagnosis of recurrenceDistant lymph nodesSingle-institution studyLevels of ctDNACtDNA assessmentCtDNA levelsDistant diseaseCtDNA testingPostoperative recurrenceRecurrent casesLymph nodesMonths postsurgeryDisease sitesResectionRecurrenceDNA assessmentPatientsCRC metastasisPreliminary efficacy and safety of fruquintinib as maintenance therapy after first-line treatment in metastatic colorectal cancer (mCRC): A multicenter, randomized, open-label clinical trial (the FRONT study).
Xu X, Yu Y, Liu Q, Wang Y, Cui Y, Li W, Li Q, Feng Y, Liang L, Yu S, Lv M, Liu T. Preliminary efficacy and safety of fruquintinib as maintenance therapy after first-line treatment in metastatic colorectal cancer (mCRC): A multicenter, randomized, open-label clinical trial (the FRONT study). Journal Of Clinical Oncology 2024, 42: 126-126. DOI: 10.1200/jco.2024.42.3_suppl.126.Peer-Reviewed Original ResearchProgression-free survivalMetastatic colorectal cancerDisease control rateFirst-line treatmentMedian progression-free survivalSafety of fruquintinibHand-foot syndromeFull analysis setMaintenance therapyPer-protocol setOral mucositisFR groupLeft-sided metastatic colorectal cancerOutcomes of progression-free survivalRight-sided metastatic colorectal cancerResponse to first-line treatmentClinical trialsFirst-line standard treatmentInteractive web response systemOpen-label clinical trialFirst-line therapyWeb response systemDiscontinuation of treatmentModerate dose levelsRandomized clinical trialsUnveiling the prognostic significance of malignant ascites in advanced gastrointestinal cancers: a marker of peritoneal carcinomatosis burden
Provenzano L, Gwee Y, Conca V, Lonardi S, Bozzarelli S, Tamburini E, Passardi A, Zaniboni A, Tosi F, Aprile G, Nasca V, Boccaccino A, Ambrosini M, Vetere G, Carullo M, Guaglio M, Battaglia L, Zhao J, Chia D, Yong W, Tan P, So J, Kim G, Shabbir A, Ong C, Casella F, Cremolini C, Bencivenga M, Sundar R, Pietrantonio F. Unveiling the prognostic significance of malignant ascites in advanced gastrointestinal cancers: a marker of peritoneal carcinomatosis burden. Therapeutic Advances In Medical Oncology 2024, 16: 17588359241289517. PMID: 39502404, PMCID: PMC11536604, DOI: 10.1177/17588359241289517.Peer-Reviewed Original ResearchMetastatic colorectal cancerMetastatic gastric cancerMetastatic gastric cancer patientsPeritoneal metastasisMalignant ascitesAdvanced gastrointestinal cancerSurvival outcomesMedian peritoneal cancer index scoreGastrointestinal cancerPeritoneal cancer index scoreGastric cancerMetastatic colorectal cancer patientsSubgroup of patientsMedian OSProgression-freeOverall survivalSystemic therapyPrognostic significancePatient survivalAscites groupPoor outcomeRetrospective analysisColorectal cancerRandomized trialsAscites
2023
593P Role of circulating tumor DNA (ctDNA) in assessing primary anti–epidermal growth factor receptor (EGFR) resistance in untreated RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC) patients (pts)
Loh J, Choo J, Sooi K, Low P, Ang C, Sundar R, Walsh R, Wijaya S, Low J, Hsing S, Jain S, Chee C. 593P Role of circulating tumor DNA (ctDNA) in assessing primary anti–epidermal growth factor receptor (EGFR) resistance in untreated RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC) patients (pts). Annals Of Oncology 2023, 34: s429. DOI: 10.1016/j.annonc.2023.09.1784.Peer-Reviewed Original ResearchQuantitative 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 markersColorectal cancer: Review of signaling pathways and associated therapeutic strategies
Leiphrakpam P, Rajappa S, Krishnan M, Batra R, Murthy S, Are C. Colorectal cancer: Review of signaling pathways and associated therapeutic strategies. Journal Of Surgical Oncology 2023, 127: 1277-1295. PMID: 37222698, DOI: 10.1002/jso.27295.Peer-Reviewed Original ResearchAnalysis of the impact of eliminating bolus 5-fluorouracil in metastatic colorectal cancer.
Peng C, Saffo S, Shusterman M, Becker D, Berlin J, Oberstein P, Nagar A, Yu S. Analysis of the impact of eliminating bolus 5-fluorouracil in metastatic colorectal cancer. Journal Of Clinical Oncology 2023, 41: 59-59. DOI: 10.1200/jco.2023.41.4_suppl.59.Peer-Reviewed Original ResearchMetastatic colorectal cancerOverall survivalECOG scoreColorectal cancerUnivariable Cox proportional hazards modelsFirst-line treatment regimensCox proportional hazards modelHigh-risk comorbiditiesHigher ECOG scoreRole of bolusMulticenter cohort studyOverall survival benefitRisk of deathLimited functional statusCombination drug regimenProportional hazards modelUse of bolusPropensity-score matchingAdjuvant settingBaseline creatinineFlatiron HealthMedian followCohort studyCreatinine levelsDrug regimen
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