2024
Devimistat (CPI-613) With Modified Fluorouarcil, Oxaliplatin, Irinotecan, and Leucovorin (FFX) Versus FFX for Patients With Metastatic Adenocarcinoma of the Pancreas: The Phase III AVENGER 500 Study.
Philip P, Sahai V, Bahary N, Mahipal A, Kasi A, Rocha Lima C, Alistar A, Oberstein P, Golan T, Metges J, Lacy J, Fountzilas C, Lopez C, Ducreux M, Hammel P, Salem M, Bajor D, Benson A, Luther S, Pardee T, Van Cutsem E. Devimistat (CPI-613) With Modified Fluorouarcil, Oxaliplatin, Irinotecan, and Leucovorin (FFX) Versus FFX for Patients With Metastatic Adenocarcinoma of the Pancreas: The Phase III AVENGER 500 Study. Journal Of Clinical Oncology 2024, jco2302659. PMID: 39088774, DOI: 10.1200/jco.23.02659.Peer-Reviewed Original ResearchMetastatic pancreatic adenocarcinomaOverall survivalCPI-613Randomized phase III trialTreatment-emergent adverse eventsExperimental armDifficult-to-treat diseaseFavorable performance statusProgression-free survivalTreatment naive patientsFirst-line therapyPhase I studyPhase III trialsMedian OSMetastatic adenocarcinomaIII trialsFirst-linePerformance statusPancreatic adenocarcinomaAdverse eventsDevimistatDay 1Disease progressionControl armPatients
2023
Pre-operative chemoradiotherapy with or without induction chemotherapy for operable locally-advanced esophageal cancer
Peters G, Talcott W, Peters N, Dhanasopan A, Lacy J, Cecchini M, Kortmansky J, Stein S, Lattanzi S, Park H, Boffa D, Johung K, Jethwa K. Pre-operative chemoradiotherapy with or without induction chemotherapy for operable locally-advanced esophageal cancer. Journal Of Gastrointestinal Oncology 2023, 14: 1181-1192. PMID: 37435226, PMCID: PMC10331751, DOI: 10.21037/jgo-22-1005.Peer-Reviewed Original ResearchProgression-free survivalMedian progression-free survivalOverall survivalIC-CRTInduction chemotherapySingle-institution retrospective cohort studyPre-operative chemoradiotherapyAdvanced esophageal cancerAdvanced esophageal carcinomaPathologic complete responseRetrospective cohort studyKaplan-Meier methodSubset of patientsProportional hazards regressionCycles of inductionAdenocarcinoma histologyCRT cohortCohort studyComplete responsePathologic responseTreatment cohortsDistant metastasisHazards regressionEsophageal cancerEsophageal carcinomaEffect of a MUC5AC Antibody (NPC-1C) Administered With Second-Line Gemcitabine and Nab-Paclitaxel on the Survival of Patients With Advanced Pancreatic Ductal Adenocarcinoma
Huffman B, Mallick A, Horick N, Wang-Gillam A, Hosein P, Morse M, Beg M, Murphy J, Mavroukakis S, Zaki A, Schlechter B, Sanoff H, Manz C, Wolpin B, Arlen P, Lacy J, Cleary J. Effect of a MUC5AC Antibody (NPC-1C) Administered With Second-Line Gemcitabine and Nab-Paclitaxel on the Survival of Patients With Advanced Pancreatic Ductal Adenocarcinoma. JAMA Network Open 2023, 6: e2249720. PMID: 36602796, PMCID: PMC9856813, DOI: 10.1001/jamanetworkopen.2022.49720.Peer-Reviewed Original ResearchConceptsAdvanced pancreatic ductal adenocarcinomaPancreatic ductal adenocarcinomaObjective response rateProgression-free survivalSecond-line treatmentNab-paclitaxelOverall survivalClinical trialsDuctal adenocarcinomaRandomized phase II clinical trialMedian progression-free survivalGemcitabine/nab-paclitaxelCox proportional hazards analysisEnd pointPhase II clinical trialChemotherapy dose reductionsFirst-line FOLFIRINOXSecond-line gemcitabineMedian overall survivalPrimary end pointSecondary end pointsProportional hazards analysisSurvival of patientsLow performance statusPretreatment clinical variables
2022
Phase 3, multicenter, randomized study of CPI-613 with modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) as first-line therapy for patients with metastatic adenocarcinoma of the pancreas (AVENGER500).
Philip P, Bahary N, Mahipal A, Kasi A, Rocha Lima C, Alistar A, Oberstein P, Golan T, Sahai V, Metges J, Lacy J, Fountzilas C, Lopez C, Ducreux M, Hammel P, Salem M, Bajor D, Benson A, Buyse M, Van Cutsem E. Phase 3, multicenter, randomized study of CPI-613 with modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) as first-line therapy for patients with metastatic adenocarcinoma of the pancreas (AVENGER500). Journal Of Clinical Oncology 2022, 40: 4023-4023. DOI: 10.1200/jco.2022.40.16_suppl.4023.Peer-Reviewed Original ResearchProgression-free survivalMetastatic pancreatic cancerOverall response rateMedian overall survivalFirst-line therapyCPI-613Experimental armRandomized phase 3 trialStandard first-line therapyTreatment-emergent adverse eventsDoses of irinotecanTreatment-naïve patientsPhase 3 trialDuration of responseLimited treatment optionsPatient reported outcomesTest armIntolerable toxicityPrimary endpointSecondary endpointsAdverse eventsOverall survivalMetastatic adenocarcinomaTreatment optionsControl arm
2021
Clinical outcomes of first line FOLFIRINOX vs . gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System
Patel T, Miccio J, Cecchini M, Srikumar T, Stein S, Kortmanksy J, Johung K, Lacy J. Clinical outcomes of first line FOLFIRINOX vs . gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System. Journal Of Gastrointestinal Oncology 2021, 0: 0-0. PMID: 35070386, PMCID: PMC8748034, DOI: 10.21037/jgo-21-202.Peer-Reviewed Original ResearchMetastatic pancreatic cancerFirst-line FOLFIRINOXTreatment discontinuationFFX groupDose modificationOverall survivalNab-paclitaxelPancreatic cancerGN groupComparative effectivenessMedian TTDFirst-line settingMedian overall survivalOutcomes of patientsTreatment-related toxicityFirst-line therapyKaplan-Meier methodRate of hospitalizationElectronic medical record systemAdjuvant gemcitabineChemotherapy toxicityDiscontinuation ratesLine therapyMedical record systemTreatment toxicity
2020
Microsatellite instability and KRAS mutation in stage 4 CRC: Prevalence, geographic discrepancies and outcomes from the National Cancer Database.
Uhlig J, Cecchini M, Stein S, Lacy J, Kim K. Microsatellite instability and KRAS mutation in stage 4 CRC: Prevalence, geographic discrepancies and outcomes from the National Cancer Database. Journal Of Clinical Oncology 2020, 38: e16052-e16052. DOI: 10.1200/jco.2020.38.15_suppl.e16052.Peer-Reviewed Original ResearchNational Cancer DatabaseOverall survivalKRAS statusKRAS mutationsMicrosatellite instabilityMicrosatellite statusCancer DatabaseCRC siteStage IV colorectal adenocarcinomaStage IV CRC patientsUnited States National Cancer DatabaseCox proportional hazards modelStage IV CRCKRAS mutation rateRight-sided CRCProportional hazards modelDistinct prognostic profilesStatistical interaction testsKRAS wildtypePatient demographicsCRC patientsMetastatic burdenCRC treatmentMultivariable analysisPrognostic profileNeuroendocrine and carcinoid tumors of the gastrointestinal tract: Epidemiology and outcomes from the National Cancer Database.
Uhlig J, Nie J, Stein S, Cecchini M, Lacy J, Kim H. Neuroendocrine and carcinoid tumors of the gastrointestinal tract: Epidemiology and outcomes from the National Cancer Database. Journal Of Clinical Oncology 2020, 38: 609-609. DOI: 10.1200/jco.2020.38.4_suppl.609.Peer-Reviewed Original ResearchNational Cancer DatabaseNeuroendocrine tumorsOverall survivalSmall intestineSurgical resectionYounger patientsCancer DatabaseGastrointestinal tractImproved overall survivalPrimary disease siteLonger overall survivalPrimary cancer siteProportional hazards modelAfrican AmericansLower stageConcurrent chemotherapyMultivariable adjustmentAdult patientsMost metastasesPatient agePatient demographicsIndependent prognosticatorCarcinoid tumorsHepatic metastasesTumor sizeHALO 109-301: A randomized, double-blind, placebo-controlled, phase 3 study of pegvorhyaluronidase alfa (PEGPH20) + nab-paclitaxel/gemcitabine (AG) in patients (pts) with previously untreated hyaluronan (HA)-high metastatic pancreatic ductal adenocarcinoma (mPDA).
Tempero M, Van Cutsem E, Sigal D, Oh D, Fazio N, Macarulla T, Hitre E, Hammel P, Hendifar A, Bates S, Li C, De La Fouchardiere C, Heinemann V, Maraveyas A, Bahary N, Layos L, Sahai V, Zheng L, Lacy J, Bullock A. HALO 109-301: A randomized, double-blind, placebo-controlled, phase 3 study of pegvorhyaluronidase alfa (PEGPH20) + nab-paclitaxel/gemcitabine (AG) in patients (pts) with previously untreated hyaluronan (HA)-high metastatic pancreatic ductal adenocarcinoma (mPDA). Journal Of Clinical Oncology 2020, 38: 638-638. DOI: 10.1200/jco.2020.38.4_suppl.638.Peer-Reviewed Original ResearchMetastatic pancreatic ductal adenocarcinomaObjective response rateProgression-free survivalPhase 3 studyOverall survivalAdverse eventsTumor microenvironmentHazard ratioNab-paclitaxel/gemcitabineRandomized phase 2 studyMedian progression-free survivalIntolerable adverse eventsMedian overall survivalPhase 2 studyPancreatic ductal adenocarcinomaPegvorhyaluronidase alfaProphylactic enoxaparinRECIST v1.1Primary endpointSecondary endpointsTE eventsBaseline characteristicsMusculoskeletal eventsThromboembolism riskClinical outcomes
2019
KRAS mutation and microsatellite instability in colorectal cancer: Screening pattern and mutational landscape across the US.
Uhlig J, Stein S, Lacy J, Kim H. KRAS mutation and microsatellite instability in colorectal cancer: Screening pattern and mutational landscape across the US. Journal Of Clinical Oncology 2019, 37: e15138-e15138. DOI: 10.1200/jco.2019.37.15_suppl.e15138.Peer-Reviewed Original ResearchOverall survivalColorectal cancerKRAS mutationsMicrosatellite instabilityNon-metastatic colorectal cancerPropensity scoreCox proportional hazards modelMetastatic colorectal cancerNational Cancer DatabasePatients' overall survivalProportional hazards modelMutational screeningDistinct mutational patternsPatient ageYounger patientsMutational prevalenceCancer DatabaseCancer factorsCRC siteFemale African AmericansHazards modelAcademic centersEast South CentralPatientsFemale Caucasians
2018
The effect of socioeconomic factors on the outcome of intrahepatic cholangiocarcinoma.
Sellers C, Ludwig J, Uhlig J, Stein S, Lacy J, Kim H. The effect of socioeconomic factors on the outcome of intrahepatic cholangiocarcinoma. Journal Of Clinical Oncology 2018, 36: 465-465. DOI: 10.1200/jco.2018.36.4_suppl.465.Peer-Reviewed Original ResearchMedian overall survivalOverall survivalIntrahepatic cholangiocarcinomaPrimary insurancePrivate insuranceLocoregional therapyInner-city tertiary care hospitalDecreased median overall survivalCox proportional hazard modelingCancer-directed treatmentOS of patientsTertiary care hospitalKaplan-Meier curvesProportional hazard modelingPrivate insurance patientsSocioeconomic factorsConsecutive patientsCare hospitalCancer RegistryMean ageTreatment coursePreventive careEarly treatmentMedicaid patientsInsurance patientsA phase IB/II randomized study of mFOLFIRINOX (mFFOX) + pegylated recombinant human hyaluronidase (PEGPH20) versus mFFOX alone in patients with good performance status metastatic pancreatic adenocarcinoma (mPC): SWOG S1313 (NCT #01959139).
Ramanathan R, McDonough S, Philip P, Hingorani S, Lacy J, Kortmansky J, Thumar J, Chiorean E, Shields A, Behl D, Mehan P, Gaur R, Seery T, Guthrie K, Hochster H. A phase IB/II randomized study of mFOLFIRINOX (mFFOX) + pegylated recombinant human hyaluronidase (PEGPH20) versus mFFOX alone in patients with good performance status metastatic pancreatic adenocarcinoma (mPC): SWOG S1313 (NCT #01959139). Journal Of Clinical Oncology 2018, 36: 208-208. DOI: 10.1200/jco.2018.36.4_suppl.208.Peer-Reviewed Original ResearchMetastatic pancreatic adenocarcinomaPhase II studyOverall survivalII studyPhase Ib/IIProphylactic growth factor supportUntreated metastatic pancreatic adenocarcinomaRandomized phase II studyGemcitabine/nab-paclitaxelAdequate organ functionMedian overall survivalGrowth factor supportInterim futility analysisRecombinant human hyaluronidaseClinical trial informationDelivery of gemcitabineBolus 5FULMWH prophylaxisMedian OSTumor hyaluronanCombination armNab-paclitaxelPrimary endpointThromboembolic eventsStandard armRAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma.
Fuchs C, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran S, Van Cutsem E, Ilson D, Tabernero J, Chau I, Ducreux M, Mendez G, Molina Alavez A, Takahari D, Mansoor W, Lacy J, Gorbunova V, Ferry D, Lin J, Das M, Shah M. RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma. Journal Of Clinical Oncology 2018, 36: 5-5. DOI: 10.1200/jco.2018.36.4_suppl.5.Peer-Reviewed Original ResearchProgression-free survivalFirst-line chemotherapyPrimary endpointITT populationOverall survivalPlacebo-controlled phase III studyECOG performance status 0Addition of ramucirumabIgG1 human monoclonal antibodiesPerformance status 0Powered secondary endpointSecond-line treatmentTreatment-naïve patientsFirst-line therapyNew safety signalsPhase III studyGastroesophageal junction adenocarcinomaSignificant clinical benefitHuman monoclonal antibodyImproved OSStatus 0Metastatic gastricSecondary endpointsAdverse eventsIII studyPhase II LAPACT trial of nab -paclitaxel ( nab -P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC).
Hammel P, Lacy J, Portales F, Sobrero A, Pazo Cid R, Manzano Mozo J, Terrebonne E, Dowden S, Shiansong Li J, Ong T, Nydam T, Philip P. Phase II LAPACT trial of nab -paclitaxel ( nab -P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC). Journal Of Clinical Oncology 2018, 36: 204-204. DOI: 10.1200/jco.2018.36.4_suppl.204.Peer-Reviewed Original ResearchProgression-free survivalDisease control rateOverall response rateTreatment failureAdverse eventsProgressive diseaseOverall survivalICS treatmentEastern Cooperative Oncology Group performance statusInvestigator's choiceGrade 3 peripheral neuropathyMedian progression-free survivalTreatment-emergent adverse eventsCycles of nabAdvanced pancreatic cancerKey secondary endpointMedian TTFTreatment-naive patientsPhase 2 trialUnacceptable adverse eventsPancreatic tumor burdenInduction therapyUnresectable LAPCInduction regimenNab-paclitaxel
2016
LAPACT: An open-label, multicenter phase II trial of nab -paclitaxel ( nab -P) plus gemcitabine (Gem) in patients (pts) with locally advanced pancreatic cancer (LAPC).
Philip P, Lacy J, Dowden S, Sastre J, Bathini V, Cardin D, Ma W, Sobrero A, Koski S, Borg C, Tonini G, Rivera F, Hwang J, Knoble J, Al Baghdadi T, Saif W, Meiri E, Kayitalire L, Li J, Hammel P. LAPACT: An open-label, multicenter phase II trial of nab -paclitaxel ( nab -P) plus gemcitabine (Gem) in patients (pts) with locally advanced pancreatic cancer (LAPC). Journal Of Clinical Oncology 2016, 34: tps477-tps477. DOI: 10.1200/jco.2016.34.4_suppl.tps477.Peer-Reviewed Original ResearchCycles of nabDisease control rateProgressive diseaseOverall survivalEastern Cooperative Oncology Group performance statusMulticenter phase II trialPhase III MPACT trialAdequate organ functionAdvanced pancreatic cancerCycles of therapySafety of nabEffective systemic therapyImproved local controlPhase II trialProgression-free survivalLonger overall survivalOverall response rateQuality of lifeMedian TTFMPACT trialSignificant ascitesUnresectable LAPCExploratory endpointsPrimary endpointSecondary endpoints
2014
Second-line gemcitabine plus nab-paclitaxel (G+A) for advanced pancreatic cancer (APC) after first-line FOLFIRINOX: Single institution retrospective review of efficacy and toxicity.
Zhang Y, Hochster H, Stein S, Lacy J. Second-line gemcitabine plus nab-paclitaxel (G+A) for advanced pancreatic cancer (APC) after first-line FOLFIRINOX: Single institution retrospective review of efficacy and toxicity. Journal Of Clinical Oncology 2014, 32: 344-344. DOI: 10.1200/jco.2014.32.3_suppl.344.Peer-Reviewed Original ResearchAdvanced pancreatic cancerTreatment failureOverall survivalRetrospective reviewDose reductionActive first-line regimenSingle-institution retrospective reviewFirst-line FOLFIRINOXInitial dose reductionSecond-line gemcitabineYale Cancer CenterFirst-line regimenSingle institution experienceDose densityFurther dose reductionPaucity of dataECOG PSHematologic toxicityLine regimenNab-paclitaxelUnacceptable toxicityInstitution experienceCA 19Cancer CenterPancreatic cancer
2013
Phase II study of mFOLFOX with bevacizumab (Bev) in metastatic gastroesophageal and gastric (GE) adenocarcinoma (AC).
Li J, Kortmansky J, Fischbach N, Stein S, Yao X, Hochster H, Lacy J. Phase II study of mFOLFOX with bevacizumab (Bev) in metastatic gastroesophageal and gastric (GE) adenocarcinoma (AC). Journal Of Clinical Oncology 2013, 31: 4084-4084. DOI: 10.1200/jco.2013.31.15_suppl.4084.Peer-Reviewed Original ResearchCisplatin-based regimensOverall survivalGE adenocarcinomaResponse rateMetastatic sitesProspective phase II trialECOG PS 0/1Grade 3/4 toxicitiesMedian overall survivalPhase II studyPhase II trialPhase III studyDVT/PELiver 19Median TTPPrior gastrectomyPS 0/1GI perforationHemorrhagic eventsII studyII trialIII studyMedian survivalMedian ageGastric adenocarcinoma
2012
Single institution experience with FOLFIRINOX in advanced pancreatic cancer (PC).
Gunturu K, Thumar J, Hochster H, Stein S, Yao X, Cong X, Lacy J. Single institution experience with FOLFIRINOX in advanced pancreatic cancer (PC). Journal Of Clinical Oncology 2012, 30: e14534-e14534. DOI: 10.1200/jco.2012.30.15_suppl.e14534.Peer-Reviewed Original ResearchAdvanced pancreatic cancerMetastatic pancreatic cancerPancreatic cancerOverall survivalMetastatic PCProphylactic pegfilgrastimAdvanced unresectable pancreatic cancerECOG PS 0/1Efficacy of FOLFIRINOXGrade 3/4 fatigueUnresectable pancreatic cancerYale Cancer CenterSingle institution experienceKaplan-Meier methodWarrants further evaluationDose attenuationChemotherapy 5PS 0/1Free survivalSurgical resectionUnacceptable toxicityImproved tolerabilityPhysician's discretionRetrospective reviewInstitution experience
2006
Hepatic metastasectomy following FOLFOX therapy in patients with colorectal metastases
Arciero C, Salem R, Lacy J, Sigurdson E, Hoffman J, Watson J, Joseph N, Cooper H, Meropol N, Burtness B. Hepatic metastasectomy following FOLFOX therapy in patients with colorectal metastases. Journal Of Clinical Oncology 2006, 24: 13523-13523. DOI: 10.1200/jco.2006.24.18_suppl.13523.Peer-Reviewed Original ResearchHepatic metastasectomyPathologic complete responseFOLFOX chemotherapySynchronous metastasesAdverse prognostic featuresHigher lesion numberMedian age 55Multiple wedge resectionsTumor size 1Portal lymph nodesMetastatic colon cancerResidual cancer cellsCurative intentMedian followColorectal metastasesFOLFOX therapyOverall survivalOxaliplatin chemotherapyPathologic responseRadiographic responseResidual cancerSystemic therapyWedge resectionComplete resectionComplete response