2023
Mismatch repair deficiency, next-generation sequencing-based microsatellite instability, and tumor mutational burden as predictive biomarkers for immune checkpoint inhibitor effectiveness in frontline treatment of advanced stage endometrial cancer
Hill B, Graf R, Shah K, Danziger N, Lin D, Quintanilha J, Li G, Haberberger J, Ross J, Santin A, Slomovitz B, Elvin J, Eskander R. Mismatch repair deficiency, next-generation sequencing-based microsatellite instability, and tumor mutational burden as predictive biomarkers for immune checkpoint inhibitor effectiveness in frontline treatment of advanced stage endometrial cancer. International Journal Of Gynecological Cancer 2023, 33: 504-513. PMID: 36750267, PMCID: PMC10086481, DOI: 10.1136/ijgc-2022-004026.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorColorectal NeoplasmsDNA Mismatch RepairEndometrial NeoplasmsFemaleHigh-Throughput Nucleotide SequencingHumansImmune Checkpoint InhibitorsMicrosatellite InstabilityConceptsImmune checkpoint inhibitorsAdvanced endometrial cancerTumor mutational burdenAdjusted hazard ratioEndometrial cancerCheckpoint inhibitorsOverall survivalMismatch repair deficiencyFrontline treatmentMicrosatellite instabilityMutational burdenNext treatmentTreatment discontinuationSingle-agent immune checkpoint inhibitorsAdvanced stage endometrial cancerImmune checkpoint inhibitor effectivenessImmune checkpoint inhibitor monotherapyImmune checkpoint inhibitor treatmentCox proportional hazards modelCheckpoint inhibitor monotherapyStage endometrial cancerPhase III trialsRepair deficiencyCheckpoint inhibitor treatmentLog-rank test
2022
Immune checkpoint inhibitors for recurrent endometrial cancer
Mutlu L, Harold J, Tymon-Rosario J, Santin AD. Immune checkpoint inhibitors for recurrent endometrial cancer. Expert Review Of Anticancer Therapy 2022, 22: 249-258. PMID: 35176955, DOI: 10.1080/14737140.2022.2044311.Peer-Reviewed Original ResearchMeSH KeywordsEndometrial NeoplasmsFemaleHumansImmune Checkpoint InhibitorsImmunotherapyMicrosatellite InstabilityNeoplasm Recurrence, LocalProgrammed Cell Death 1 ReceptorTumor MicroenvironmentConceptsImmune checkpoint inhibitorsRecurrent endometrial cancerCheckpoint inhibitorsEndometrial cancerEC patientsAdvanced/recurrent endometrial cancerPD-1/PD-L1 inhibitorsRecurrent EC patientsUse of chemotherapyCommon gynecologic malignancyMajor clinical trialsPD-L1 inhibitorsBiomarkers of responseViable treatment optionHuman cancer treatmentTumor microenvironment immunosuppressionRecurrent diseaseGynecologic malignanciesPD-1Clinical efficacyPatient populationTreatment optionsTumor immunogenicityRecent trialsClinical trials
2021
A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability
Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Silasi D, Huang GS, Andikyan V, Damast S, Clark M, Azodi M, Schwartz PE, Tymon‐Rosario J, Harold JA, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Alexandrov LB, Iwasaki A, Kong Y, Song E, Dong W, Elvin JA, Choi J, Santin AD. A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability. Cancer 2021, 128: 1206-1218. PMID: 34875107, PMCID: PMC9465822, DOI: 10.1002/cncr.34025.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedDNA Mismatch RepairEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityNeoplasm Recurrence, LocalPilot ProjectsProspective StudiesConceptsObjective response rateImmune checkpoint inhibitorsProgression-free survivalEndometrial cancerWhole-exome sequencingSporadic endometrial cancerOverall survivalEnd pointPhase 2 pilot studyPrimary end pointSecondary end pointsTumor mutation burdenPhase 2 evaluationLarger confirmatory studiesAntigen processing/presentationProcessing/presentationCheckpoint inhibitorsSurgical resectionICI resistanceDMMR patientsPrognostic significanceDMMR tumorsMechanisms of resistanceLocal treatmentSporadic MSIA phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793)
Bellone S, Roque DM, Siegel ER, Buza N, Hui P, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Silasi D, Huang GS, Andikyan V, Damast S, Clark M, Azodi M, Schwartz PE, Tymon-Rosario J, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Alexandrov LB, Iwasaki A, Kong Y, Song E, Dong W, Elvin J, Choi J, Santin AD. A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793). Annals Of Oncology 2021, 32: 1045-1046. PMID: 33932502, PMCID: PMC9465821, DOI: 10.1016/j.annonc.2021.04.013.Commentaries, Editorials and Letters
2016
Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro
Bellone S, Bignotti E, Lonardi S, Ferrari F, Centritto F, Masserdotti A, Pettinella F, Black J, Menderes G, Altwerger G, Hui P, Lopez S, de Haydu C, Bonazzoli E, Predolini F, Zammataro L, Cocco E, Ferrari F, Ravaggi A, Romani C, Facchetti F, Sartori E, Odicino FE, Silasi DA, Litkouhi B, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro. Gynecologic Oncology 2016, 144: 146-152. PMID: 27894751, PMCID: PMC5183545, DOI: 10.1016/j.ygyno.2016.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsCarboplatinCarcinomaCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell SurvivalDisease-Free SurvivalDNA Polymerase IIDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityMiddle AgedMutationPoly-ADP-Ribose Binding ProteinsTumor Cells, CulturedConceptsBetter prognosisTumor cell linesInfiltration of CD4Number of CD4Platinum-based chemotherapyT lymphocyte infiltrationPD-1 receptorCell linesLow metastatic capabilityPOLE-mutated tumorsWild-type ECsEC cell linesLymphocyte infiltrationFavorable prognosisPD-1EC patientsType tumorsEnhanced immunogenicityT lymphocytesMolecular subtypesTumors correlatesChemotherapyMetastatic capabilityPrognosisTumors