2024
Unmet needs in cervical cancer – can biological therapies plug the gap?
Greenman M, Chang Y, McNamara B, Mutlu L, Santin A. Unmet needs in cervical cancer – can biological therapies plug the gap? Expert Opinion On Biological Therapy 2024, 24: 995-1003. PMID: 39311611, DOI: 10.1080/14712598.2024.2408754.Peer-Reviewed Original ResearchBiologic therapyCervical cancerIntroduction of biologic therapiesManagement of cervical cancerImmune checkpoint inhibitorsIncreased overall survivalCurrent treatment recommendationsMultiple tumor typesAntibody-drug conjugatesCheckpoint inhibitorsOverall survivalRecurrent diseaseGynecologic malignanciesTreat malignanciesTumor typesClinical outcomesAngiogenesis inhibitorsBurden of casesTreatment recommendationsTherapyImprove current standardsAntitumor activityInadequate screeningCancerMalignancyRandomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses
Roque D, Siegel E, Buza N, Bellone S, Huang G, Altwerger G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Ratner E, Santin A. Randomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses. BJC Reports 2024, 2: 43. PMID: 39516558, PMCID: PMC11523995, DOI: 10.1038/s44276-024-00067-5.Peer-Reviewed Original ResearchPre-treated ovarian cancerOverall survivalBev armsDose reductionOvarian cancerTaxane responseRandomized phase 2 trialRandomized phase II trialPaclitaxel-resistant diseaseResultsThirty-seven patientsTreated with paclitaxelPhase 2 trialBiweekly bevacizumabDays 1,8,15Taxane-sensitiveUpdate survivalProgression-freePeritoneal cancerDose modificationTaxane sensitivityPlatinum resistanceSubset analysisSubgroup analysisResponse ratePatients
2023
In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma.
Mutlu L, Manavella D, Bellone S, McNamara B, Harold J, Mauricio D, Siegel E, Buza N, Hui P, Hartwich T, Yang-Hartwich Y, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma. Molecular Cancer Therapeutics 2023, 22: 1404-1412. PMID: 37676984, DOI: 10.1158/1535-7163.mct-23-0126.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityT-DXdUSC patientsUSC cell linesTrastuzumab deruxtecanSerous carcinomaHER2 expressionClinical trialsRecurrent uterine serous carcinomaTopoisomerase I inhibitor payloadSignificant antibody-dependent cellular cytotoxicityCell linesMultiple tumor indicationsPrimary USC cell linesLow HER2 expressionFuture clinical trialsHigh recurrence ratePeripheral blood lymphocytesERBB2 gene amplificationGrowth suppressionHER2-overexpressing cell linesTumor growth suppressionOverall survivalStandard chemotherapyMonitoring Treatment Response, Early Recurrence, and Survival in Uterine Serous Carcinoma and Carcinosarcoma Patients Using Personalized Circulating Tumor DNA Biomarkers
Bellone S, McNamara B, Mutlu L, Demirkiran C, Hartwich T, Harold J, Yang-Hartwich Y, Siegel E, Santin A. Monitoring Treatment Response, Early Recurrence, and Survival in Uterine Serous Carcinoma and Carcinosarcoma Patients Using Personalized Circulating Tumor DNA Biomarkers. International Journal Of Molecular Sciences 2023, 24: 8873. PMID: 37240216, PMCID: PMC10219151, DOI: 10.3390/ijms24108873.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaCS patientsEarly recurrenceDroplet digital polymerase chain reactionCA 125Serous carcinomaCtDNA testingTime of surgeryTime of recurrenceReliable tumor biomarkersTumour DNA biomarkersCarcinosarcoma patientsUSC patientsRecurrent diseaseOccult diseaseOverall survivalEndometrial cancerAggressive variantInitial treatmentRecurrent tumorsResidual tumorClinical findingsTreatment courseTreatment trialsPIK3CA mutationsLenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775
Makker V, Colombo N, Herráez A, Monk B, Mackay H, Santin A, Miller D, Moore R, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim Y, Alia E, Sanli U, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. Journal Of Clinical Oncology 2023, 41: 2904-2910. PMID: 37058687, PMCID: PMC10414727, DOI: 10.1200/jco.22.02152.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalPrimary end pointAdvanced endometrial cancerOverall survivalEndometrial cancerEnd pointMismatch repair-proficient tumorsClinical trial updateMetastatic endometrial cancerNew safety signalsSubgroups of interestManageable safetyPrespecified analysisTrial updateProficient tumorsClinical trialsSafety signalsPembrolizumabLenvatinibPhysician's choiceMultiple end pointsResponse rateSecondary analysisChemotherapyUterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Yang K, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Burton E, Inagaki H, Albers A, Zhang C, Bollag G, Schlessinger J, Santin A. Uterine leiomyosarcomas harboring MAP2K4 gene amplification are sensitive in vivo to PLX8725, a novel MAP2K4 inhibitor. Gynecologic Oncology 2023, 172: 65-71. PMID: 36958197, PMCID: PMC10192120, DOI: 10.1016/j.ygyno.2023.03.009.Peer-Reviewed Original ResearchConceptsUterine leiomyosarcomaPDX modelsGain of functionMedian overall survivalPhase I trialOral gavage dailyVivo activityTumor growth inhibitionTumor volume differencesTumor cell proliferationOverall survivalTolerable toxicityI trialOral treatmentTreatment cohortsGavage dailyAggressive tumorsSCID miceULMS patientsPK studiesTumor samplesWestern blotCell proliferationControl vehicleLeiomyosarcomaMismatch 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
Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma
Harold J, Bellone S, Manavella D, Mutlu L, McNamara B, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Santin A. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Gynecologic Oncology 2022, 168: 157-165. PMID: 36442427, PMCID: PMC9797429, DOI: 10.1016/j.ygyno.2022.11.014.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsUterine leiomyosarcomaVivo activityVehicle control treatmentMedian overall survivalTumor volume differencesOral scheduleWestern blot analysisOverall survivalOral gavageAggressive malignancyPDX modelsClinical trialsSCID miceTumor measurementsULMS patientsSignificant growth inhibitionNovel ATR inhibitorTumor samplesSignificant toxicityWestern blotKinase inhibitorsATRX mutationsGene mutationsControl vehicleLenvatinib plus Pembrolizumab for Advanced Endometrial Cancer
Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. New England Journal Of Medicine 2022, 386: 437-448. PMID: 35045221, DOI: 10.1056/nejmoa2108330.Peer-Reviewed Original ResearchConceptsAdvanced endometrial cancerProgression-free survivalEndometrial cancerOverall survivalMedian progression-free survivalPlatinum-based chemotherapy regimenLonger progression-free survivalEnd pointBlinded independent central reviewMedian overall survivalPrimary end pointPhase 3 trialResponse Evaluation CriteriaPlatinum-based chemotherapyIndependent central reviewChemotherapy regimenAdverse eventsStandard therapyCentral reviewPembrolizumabGrade 3LenvatinibChemotherapyPhysician's choicePatients
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 status
2020
Randomized Phase II Trial of Carboplatin–Paclitaxel Compared with Carboplatin–Paclitaxel–Trastuzumab in Advanced (Stage III–IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis
Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers S, Secord AA, Havrilesky L, O'Malley DM, Backes FJ, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi K, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin–Paclitaxel Compared with Carboplatin–Paclitaxel–Trastuzumab in Advanced (Stage III–IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clinical Cancer Research 2020, 26: 3928-3935. PMID: 32601075, PMCID: PMC8792803, DOI: 10.1158/1078-0432.ccr-20-0953.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsCarboplatinChemotherapy, AdjuvantCystadenocarcinoma, SerousCytoreduction Surgical ProceduresDrug Administration ScheduleEndometrial NeoplasmsEndometriumFemaleFollow-Up StudiesHumansMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPaclitaxelProgression-Free SurvivalReceptor, ErbB-2Survival AnalysisTrastuzumabConceptsProgression-free survivalRandomized phase II trialPhase II trialOverall survivalHER2/neuStage IIICarboplatin-paclitaxelII trialRecurrent diseaseControl armSurvival analysisRecurrent uterine serous carcinomaCarboplatin/paclitaxelUterine serous carcinomaOverall survival analysisEvaluable patientsEligible patientsPrimary endpointSecondary endpointsEndometrial cancerAggressive variantSerous carcinomaPrimary treatmentSurvival medianPatientsNeratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial
Oaknin A, Friedman CF, Roman LD, D’Souza A, Brana I, Bidard F, Goldman J, Alvarez EA, Boni V, ElNaggar AC, Passalacqua R, T.M. K, Santin AD, Keyvanjah K, Xu F, Eli LD, Lalani AS, Bryce RP, Hyman DM, Meric-Bernstam F, Solit DB, Monk BJ. Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial. Gynecologic Oncology 2020, 159: 150-156. PMID: 32723675, PMCID: PMC8336424, DOI: 10.1016/j.ygyno.2020.07.025.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultDiarrheaFemaleHumansKaplan-Meier EstimateMiddle AgedMutationNauseaNeoplasm Recurrence, LocalProgression-Free SurvivalProtein Kinase InhibitorsQuinolinesReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsSeverity of Illness IndexUterine Cervical NeoplasmsConceptsProgression-free survivalClinical benefit rateObjective response rateCervical cancerOverall survivalHER2 mutationsBasket trialsMetastatic/recurrent cervical cancerAdvanced/recurrent diseaseMedian progression-free survivalCommon HER2 mutationsGrade 3 diarrheaGrade 4 eventsHER2-mutant cancersSafety of neratinibCommon adverse eventsMedian overall survivalRecurrent cervical cancerMetastatic cervical cancerNew safety signalsPhase II basket trialPlatinum-based treatmentTyrosine kinase inhibitorsWarrants further investigationEligible patientsHuman epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study
Erickson BK, Najjar O, Damast S, Blakaj A, Tymon-Rosario J, Shahi M, Santin A, Klein M, Dolan M, Cimino-Mathews A, Buza N, Ferriss JS, Stone RL, Khalifa M, Fader AN. Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study. Gynecologic Oncology 2020, 159: 17-22. PMID: 32709539, PMCID: PMC7541557, DOI: 10.1016/j.ygyno.2020.07.016.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorChemoradiotherapy, AdjuvantCystadenocarcinoma, SerousFemaleFollow-Up StudiesHumansHysterectomyImmunohistochemistryMiddle AgedNeoplasm InvasivenessNeoplasm Recurrence, LocalNeoplasm StagingPrognosisProgression-Free SurvivalReceptor, ErbB-2Retrospective StudiesRisk AssessmentUnited StatesUterine NeoplasmsUterusConceptsHuman epidermal growth factor 2Uterine serous carcinomaHER2-positive tumorsEarly-stage diseaseOverall survivalSerous carcinomaCohort studyHER2 positivityPositive tumorsEarly stage uterine serous carcinomaLymph-vascular space invasionRecurrent uterine serous carcinomaMulti-institutional cohort studyHuman epidermal growth factor receptor 2Multi-center cohort studyEpidermal growth factor receptor 2Epidermal growth factor 2HER2-positive cohortGrowth factor receptor 2HER2-negative tumorsEquivocal IHC resultsFactor receptor 2Inferior PFSAdjuvant therapyGrowth factor 2Stage III uterine serous carcinoma: modern trends in multimodality treatment
Li JY, Young MR, Huang G, Litkouhi B, Santin A, Schwartz PE, Damast S. Stage III uterine serous carcinoma: modern trends in multimodality treatment. Journal Of Gynecologic Oncology 2020, 31: e53. PMID: 32266802, PMCID: PMC7286763, DOI: 10.3802/jgo.2020.31.e53.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaExternal beam RTVaginal brachytherapyOverall survivalHuman epidermal growth factor receptorModern treatment eraSentinel node samplingRegional nodal recurrenceKaplan-Meier estimatesLog-rank testCox proportional hazardsExternal beam radiotherapyEpidermal growth factor receptorERA treatmentGrowth factor receptorUSC patientsFree survivalNodal recurrenceTreatment eraMultimodality treatmentPatient characteristicsPerioperative periodRegional nodalSerous carcinomaNode samplingHuman epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort.
Erickson B, Najjar O, Klein M, Shahi M, Dolan M, Cimino-Mathews A, Grandelis A, Buza N, Delaney P, Tymon-Rosario J, Santin A, Ferriss J, Stone R, Nickles Fader A. Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort. Journal Of Clinical Oncology 2020, 38: 6084-6084. DOI: 10.1200/jco.2020.38.15_suppl.6084.Peer-Reviewed Original ResearchHuman epidermal growth factor 2Uterine serous carcinomaEarly stage uterine serous carcinomaEarly-stage diseaseMulti-institutional cohortHER2-positive tumorsSerous carcinomaOverall survivalHER2 overexpressionStage ILymph-vascular space invasionHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Epidermal growth factor 2Endometrial cancer deathsHER2-positive cohortHER2-positive diseaseStage IB diseaseBreast cancer guidelinesGrowth factor receptor 2HER2-negative tumorsWorse survival outcomesKaplan-Meier analysisBody mass indexPoor prognostic tumorSacituzumab govitecan (SG) in patients (pts) with previously treated metastatic endometrial cancer (mEC): results from a phase I/II study.
Santin A, Komiya T, Goldenberg D, Sharkey R, Hong Q, Wegener W, Goswami T, Bardia A. Sacituzumab govitecan (SG) in patients (pts) with previously treated metastatic endometrial cancer (mEC): results from a phase I/II study. Journal Of Clinical Oncology 2020, 38: 6081-6081. DOI: 10.1200/jco.2020.38.15_suppl.6081.Peer-Reviewed Original ResearchMetastatic endometrial cancerObjective response rateClinical benefit rateProgression-free survivalDuration of responseMedian overall survivalSacituzumab govitecanOverall survivalTrop-2 expressionPlatinum therapyPhase I/II studySolid tumorsTrop-2Median progression-free survivalNeutrophil count decreasePrevious preclinical findingsPrior platinum therapySimilar safety profileAdvanced solid tumorsCT/MRI scansMetastatic solid tumorsLimited treatment optionsFurther clinical investigationFebrile neutropeniaPrior chemotherapyPreclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas
Lopez S, Perrone E, Bellone S, Bonazzoli E, Zeybek B, Han C, Tymon-Rosario J, Altwerger G, Menderes G, Bianchi A, Zammataro L, Manzano A, Manara P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Raspagliesi F, Angioli R, Buza N, Hui P, Bond HM, Santin AD. Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. Oncotarget 2020, 11: 560-570. PMID: 32082489, PMCID: PMC7007291, DOI: 10.18632/oncotarget.27342.Peer-Reviewed Original ResearchSacituzumab govitecanTrop-2 expressionTrop-2Ovarian carcinosarcomaWeekly intravenous administrationSignificant tumor growth inhibitionTumor growth inhibitionCS cell linesCell linesCell surface markersNegative cell linesAggressive carcinosarcomasCarcinosarcoma patientsPrimary carcinosarcomaOverall survivalPoor prognosisPreclinical activityRare cancersIntravenous administrationXenograft modelActive drugCarcinosarcomaActive metaboliteFFPE tumorsCell viability assaysPhase II evaluation of copanlisib, a selective inhibitor of Pi3kca, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG Oncology study (NRG-GY008)
Santin AD, Filiaci V, Bellone S, Ratner ES, Mathews CA, Cantuaria G, Gunderson CC, Rutledge T, Buttin BM, Lankes HA, Frumovitz M, Khleif SN, Huh WK, Birrer MJ. Phase II evaluation of copanlisib, a selective inhibitor of Pi3kca, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG Oncology study (NRG-GY008). Gynecologic Oncology Reports 2020, 31: 100532. PMID: 31934607, PMCID: PMC6951478, DOI: 10.1016/j.gore.2019.100532.Peer-Reviewed Original ResearchProgression-free survivalStable diseaseOverall survivalMixed histologyPIK3CA mutationsGrade 5 adverse eventsMedian progression-free survivalCommon grade 3Common PIK3CA mutationCTCAE version 4GOG performance statusNRG Oncology StudyMedian overall survivalObjective tumor responsePhase II trialPhase II evaluationBest overall responsePIK3CA gene mutationsPIK3CA hotspot mutationsSelective inhibitorEligible patientsMeasurable diseaseHotspot PIK3CA mutationsII trialPrimary endpoint
2019
Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study
Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, Raspagliesi F, Sonke GS, Birrer M, Provencher DM, Sehouli J, Colombo N, González-Martín A, Oaknin A, Ottevanger PB, Rudaitis V, Katchar K, Wu H, Keefe S, Ruman J, Ledermann JA. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Annals Of Oncology 2019, 30: 1080-1087. PMID: 31046082, DOI: 10.1093/annonc/mdz135.Peer-Reviewed Original ResearchConceptsRecurrent ovarian cancerObjective response rateDisease control rateProgression-free survivalTreatment-free intervalDuration of responseAdvanced recurrent ovarian cancerPD-L1 expressionPlatinum-free intervalCohort AOverall survivalPrior linesCohort BOvarian cancerHigh PD-L1 expressionLow objective response rateMedian DORSolid Tumors version 1.1End pointGynecologic cancer-related deathBlinded independent central reviewSafety of pembrolizumabSingle-agent pembrolizumabMedian overall survivalPhase II study