Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors
Choi Y, Dharia N, Jun T, Chang J, Royer-Joo S, Yau K, Assaf Z, Aimi J, Sivakumar S, Montesion M, Sacher A, LoRusso P, Desai J, Schutzman J, Shi Z, group A. Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors. Clinical Cancer Research 2024, 30: of1-of10. PMID: 38995268, PMCID: PMC11369623, DOI: 10.1158/1078-0432.ccr-24-0255.Peer-Reviewed Original ResearchConceptsKRAS G12C mutationTumor fractionSolid tumorsTumor typesG12C mutationOn-treatment time pointsNon-small cell lung cancerMutational heterogeneityAssociated with tumor typeProgression-free survivalPlasma samplesPhase 1 studyCell lung cancerCycle 1 dayAssociated with patient outcomesVariant allele frequencyAssociated with responseCtDNA levelsCtDNA profilingMetastatic sitesTruncal mutationsTumor DNATreatment responseLung cancerTumor tissuesTreatment of patients with dedifferentiated liposarcoma (DDLPS) with the MDM2–p53 antagonist brigimadlin and p53 function: A longitudinal analysis of circulating microRNAs (miRNAs) in a first-in-human phase Ia/Ib study.
Peltzer A, LoRusso P, Gounder M, Yamamoto N, Somaiah N, Lugowska I, Moreno V, Teufel M, Jayadeva G, Hesse R, Sturm G, Schöffski P. Treatment of patients with dedifferentiated liposarcoma (DDLPS) with the MDM2–p53 antagonist brigimadlin and p53 function: A longitudinal analysis of circulating microRNAs (miRNAs) in a first-in-human phase Ia/Ib study. Journal Of Clinical Oncology 2024, 42: 11540-11540. DOI: 10.1200/jco.2024.42.16_suppl.11540.Peer-Reviewed Original ResearchDedifferentiated liposarcomaP53 functionMDM2-p53Plasma samplesMiRNA analysisRestoration of p53 functionTranscription factor p53Phase Ia/Ib studyCox hazard ratio modelWild-type diseaseAdvanced solid tumorsDifferential expression analysisNext-generation sequencingBaseline plasma samplesTreatment of patientsMDM2-p53 antagonistsPlasma of patientsAnalysis of miRNAsTranscriptional regulationHsa-miR-92b-3pMDM2-amplifiedHazard ratio modelMiRNA expressionPharmacodynamic markersExpression analysisProteomic analysis in patients with dedifferentiated liposarcoma (DDLPS) in a phase Ia/Ib study of the MDM2–p53 antagonist brigimadlin.
Jaimes Y, LoRusso P, Sturm G, Gounder M, Yamamoto N, Somaiah N, Lugowska I, Moreno V, Peltzer A, Teufel M, Jayadeva G, Schöffski P. Proteomic analysis in patients with dedifferentiated liposarcoma (DDLPS) in a phase Ia/Ib study of the MDM2–p53 antagonist brigimadlin. Journal Of Clinical Oncology 2024, 42: 11541-11541. DOI: 10.1200/jco.2024.42.16_suppl.11541.Peer-Reviewed Original ResearchPhase Ia/Ib studyDedifferentiated liposarcomaDDLPS samplesTranscriptional regulation of target genesPlasma samplesPAI-1Angiopoietin-1Cycle 3 day 1Neutrophil gelatinase-associated lipocalin levelsC-C motif chemokine 5Regulation of target genesTumor suppressor p53Cox hazard ratio modelAdvanced solid tumorsProteomic analysis of plasma samplesRestore p53 activityAXL receptor tyrosine kinaseElevated GDF-15MDM2-p53 antagonistsReceptor tyrosine kinasesP53 targetsTranscriptional regulationHazard ratio modelMyelosuppression eventsP53 activationCirculating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors
Hu Y, Narayan A, Xu Y, Wolfe J, Vu D, Trinh T, Kantak C, Ivy S, Eder J, Deng Y, LoRusso P, Kim J, Patel A. Circulating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors. JCO Precision Oncology 2024, 8: e2300289. PMID: 38412387, PMCID: PMC10914240, DOI: 10.1200/po.23.00289.Peer-Reviewed Original ResearchConceptsCell-free circulating tumor DNANon-small-cell lung cancerSmall-cell lung cancerTriple-negative breast cancerPancreatic ductal adenocarcinomaAdvanced solid tumorsVariant allele fractionRadiographic responseOverall survivalCombination therapySolid tumorsCtDNA levelsLung cancerPretreated advanced solid tumorsDays of combination therapyMetastatic pancreatic ductal adenocarcinomaResponse to anticancer therapyAssociated with disease progressionProgression-free survivalPlasma samplesLead-inPoly(ADP-riboseInferior OSTumor DNASurvival outcomes