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 ResearchConceptsImmune 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
Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma.
Chow RD, Michaels T, Bellone S, Hartwich T, Bonazzoli E, Iwasaki A, Song E, Santin AD. Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma. Cancer Discovery 2022, 13: 312-331. PMID: 36301137, PMCID: PMC9905265, DOI: 10.1158/2159-8290.cd-22-0686.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsDNA Mismatch RepairEndometrial NeoplasmsFemaleHumansImmunotherapyNeoplastic Syndromes, HereditaryConceptsAnti-PD-1 immunotherapyImmune checkpoint blockadeMMRd tumorsNK cellsEndometrial carcinomaICB responseMutation burdenT-cell-driven immunityPhase II clinical trialMMRd endometrial cancersPD-1 inhibitorsMismatch repair-deficient cancersTumor-extrinsic factorsHigh response rateEffector CD8Antitumor immunityEndometrial cancerCancer immunotherapyImmune cellsLonger survivalClinical trialsPrimary resistanceT cellsResponse rateMMRd
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 ResearchConceptsObjective 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 MSIPrognostic impact of mismatch repair deficiency in high- and low-intermediate-risk, early-stage endometrial cancer following vaginal brachytherapy
Li JY, Park HS, Huang GS, Young MR, Ratner E, Santin A, Damast S. Prognostic impact of mismatch repair deficiency in high- and low-intermediate-risk, early-stage endometrial cancer following vaginal brachytherapy. Gynecologic Oncology 2021, 163: 557-562. PMID: 34602287, DOI: 10.1016/j.ygyno.2021.09.018.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalEndometrioid endometrial cancerVaginal brachytherapyPMMR patientsOverall survivalEEC patientsEndometrial cancerExact testThree-year recurrence-free survivalEarly-stage endometrial cancerCox proportional hazards regressionPoor recurrence-free survivalAdjuvant vaginal brachytherapyThree-year OSMultivariable Cox regressionLympho-vascular invasionSignificant prognostic variablesProportional hazards regressionLog-rank testKaplan-Meier estimatesDeficient mismatch repairMismatch repair statusFisher's exact testMismatch repair deficiencyDMMR statusA 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