2024
Safety and time to response of [177Lu]Lu-DOTATATE in patients with newly diagnosed advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Sub-analysis of the phase 3 randomized NETTER-2 study.
Kunz P, Ferone D, Halperin D, Myrehaug S, Herrmann K, Pavel M, Chasen B, Capdevila J, Tafuto S, Oh D, Yoo C, Falk S, Halfdanarson T, Folitar I, Zhang Y, de Herder W, Singh S. Safety and time to response of [177Lu]Lu-DOTATATE in patients with newly diagnosed advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Sub-analysis of the phase 3 randomized NETTER-2 study. Journal Of Clinical Oncology 2024, 42: 4131-4131. DOI: 10.1200/jco.2024.42.16_suppl.4131.Peer-Reviewed Original ResearchTime to responseObjective response rateGastroenteropancreatic neuroendocrine tumorsLu-DOTATATEGEP-NETsAdverse eventsHematologic toxicityNeuroendocrine tumorsSafety profileSub-analysisMedian time to responseCases of myelodysplastic syndromeOctreotide long-actingHematologic adverse eventsProgression-free survivalTime to first occurrenceRandomized treatment periodFatal adverse eventsInfection rateDose interruptionCTCAE gradeRadioligand therapyMyelodysplastic syndromeEligible ptsLaboratory abnormalitiesPhase Ib portion of the ACTION-1 phase Ib/3 trial of RYZ101 in gastroenteropancreatic neuroendocrine tumors (GEP-NET) progressing after 177Lu somatostatin analogue (SSA) therapy: Safety and efficacy findings.
Halperin D, Morris M, Ulaner G, Strosberg J, Mehr S, Li D, Soares H, Anthony L, Kotiah S, Jacene H, Tesselaar M, Kunz P, Ferreira D, Li J, Ma K, Rearden J, Moran S, Hope T, Singh S. Phase Ib portion of the ACTION-1 phase Ib/3 trial of RYZ101 in gastroenteropancreatic neuroendocrine tumors (GEP-NET) progressing after 177Lu somatostatin analogue (SSA) therapy: Safety and efficacy findings. Journal Of Clinical Oncology 2024, 42: 3091-3091. DOI: 10.1200/jco.2024.42.16_suppl.3091.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsPhase Ib portionDose-limiting toxicitySerious adverse eventsGEP-NETsSomatostatin analoguesAdverse eventsFrequent treatment-emergent adverse eventsEfficacy dataData review committeePlanned dose levelsProgression-free survivalDuration of responseGastroenteropancreatic neuroendocrine tumorsLonger-term safetyAlpha-emitting radiopharmaceuticalStandard of careDose holdRECIST v1.1Stable diseasePartial responseStarting doseTumor responseDose modificationNeuroendocrine tumors
2023
ACTION-1 phase Ib/3 trial of RYZ101 in somatostatin receptor subtype 2–expressing (SSTR2+) gastroenteropancreatic neuroendocrine tumors (GEP-NET) progressing after 177Lu somatostatin analogue (SSA) therapy: Initial safety analysis.
Morris M, Ulaner G, Halperin D, Strosberg J, Mehr S, Li D, Soares H, Anthony L, Kotiah S, Jacene H, Pavel M, Kunz P, Ferreira D, Li J, Ma K, Rearden J, Moran S, Hope T, Singh S. ACTION-1 phase Ib/3 trial of RYZ101 in somatostatin receptor subtype 2–expressing (SSTR2+) gastroenteropancreatic neuroendocrine tumors (GEP-NET) progressing after 177Lu somatostatin analogue (SSA) therapy: Initial safety analysis. Journal Of Clinical Oncology 2023, 41: 4132-4132. DOI: 10.1200/jco.2023.41.16_suppl.4132.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsAdverse eventsGEP-NETsTarget dose-limiting toxicity (DLT) rateDose de-escalation studyTreatment-related serious AEsDose-limiting toxicity rateData review committeeDe-escalation studiesECOG PS 0Phase 3 doseSomatostatin analogue therapySerious adverse eventsGastroenteropancreatic neuroendocrine tumorsStandard of careSomatostatin receptor subtypesInitial safety analysisSerious AEsAnalogue therapyPS 0Dose escalationKBq/Neuroendocrine tumorsToxicity ratesDisease progression
2022
A phase II study of sapanisertib (TAK-228) a mTORC1/2 inhibitor in rapalog-resistant advanced pancreatic neuroendocrine tumors (PNET): ECOG-ACRIN EA2161
Rajdev L, Lee JW, Libutti SK, Benson AB, Fisher GA, Kunz PL, Hendifar AE, Catalano P, O’Dwyer P. A phase II study of sapanisertib (TAK-228) a mTORC1/2 inhibitor in rapalog-resistant advanced pancreatic neuroendocrine tumors (PNET): ECOG-ACRIN EA2161. Investigational New Drugs 2022, 40: 1306-1314. PMID: 36264382, PMCID: PMC9795724, DOI: 10.1007/s10637-022-01311-w.Peer-Reviewed Original ResearchConceptsPancreatic neuroendocrine tumorsNeuroendocrine tumorsTreatment-related grade 3 adverse eventsGrade 3 adverse eventsAdvanced pancreatic neuroendocrine tumorsTwo-stage phase II trialObjective tumor responsePhase II studyPhase II trialContinuous dosing scheduleStage 1Lack of responseEligible patientsMedian OSMedian PFSII trialAdverse eventsII studyObjective responseDosing schedulesTumor responseClinical activityPatientsMTOR pathwayMTORC1/2 inhibitorsEverolimus with or without bevacizumab in advanced pNET: CALGB 80701 (Alliance).
Kulke MH, Ou FS, Niedzwiecki D, Huebner L, Kunz P, Kennecke HF, Wolin EM, Chan JA, O'Reilly EM, Meyerhardt JA, Venook A. Everolimus with or without bevacizumab in advanced pNET: CALGB 80701 (Alliance). Endocrine Related Cancer 2022, 29: 335-344. PMID: 35324465, PMCID: PMC9257687, DOI: 10.1530/erc-21-0239.Peer-Reviewed Original ResearchConceptsAdvanced pancreatic neuroendocrine tumorsProgression-free survivalPancreatic neuroendocrine tumorsVEGF pathway inhibitorsCombination armPrimary endpointMedian overall survival durationTreatment-related adverse eventsImproved progression-free survivalRandomized phase II studySuperior progression-free survivalPathway inhibitorOverall survival durationPhase II studyTreatment-related toxicityCombination of everolimusMTOR inhibitor everolimusHigh response rateAdverse eventsII studyInvestigator reviewCombination therapyStandard doseInhibitor everolimusNeuroendocrine tumors
2021
177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial
Strosberg JR, Caplin ME, Kunz PL, Ruszniewski PB, Bodei L, Hendifar A, Mittra E, Wolin EM, Yao JC, Pavel ME, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Mariani MF, Demange A, Mutevelic S, Krenning EP, investigators N. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. The Lancet Oncology 2021, 22: 1752-1763. PMID: 34793718, DOI: 10.1016/s1470-2045(21)00572-6.Peer-Reviewed Original ResearchConceptsMedian overall survivalMidgut neuroendocrine tumorsTreatment-related serious adverse eventsLong-term safety resultsFinal overall survivalPrespecified final analysisPhase 3 trialProgression-free survivalSerious adverse eventsOverall survivalLu-DOTATATE treatmentAdverse eventsNeuroendocrine tumorsLu-DOTATATESecondary endpointsLast patientMyelodysplastic syndromeSafety resultsInteractive web-based response systemControl groupAdvanced midgut neuroendocrine tumorsFinal overall survival analysisWeb-based response systemFinal analysisNETTER-1 trialTemozolomide in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicenter Retrospective Review
Chan DL, Bergsland EK, Chan JA, Gadgil R, Halfdanarson TR, Hornbacker K, Kelly V, Kunz PL, McGarrah PW, Raj NP, Reidy DL, Thawer A, Whitman J, Wu L, Becker C, Singh S. Temozolomide in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicenter Retrospective Review. The Oncologist 2021, 26: 950-955. PMID: 34342086, PMCID: PMC8571741, DOI: 10.1002/onco.13923.Peer-Reviewed Original ResearchConceptsG3 neuroendocrine neoplasmsFirst-line settingPercent of patientsMulticenter retrospective reviewTreatment failureGastroenteropancreatic neuroendocrine neoplasmsNeuroendocrine neoplasmsRetrospective reviewOptimal treatmentResponse rateGastrointestinal neuroendocrine neoplasmsLocal pathology reportsDiscontinuation of therapyMedian TTFFirst-line treatmentOverall response rateConfirmatory prospective studiesViable treatment optionPancreatic neuroendocrine neoplasmsRadiologic responseTemozolomide regimenPrimary endpointAdverse eventsMedian durationRadiographic response
2019
Temozolomide in grade III neuroendocrine neoplasms (G3 NENs): A multicenter retrospective review.
Chan D, Bergsland E, Chan J, Gadgil R, Halfdanarson T, Hornbacker K, Kelly V, Kunz P, McGarrah P, Raj N, Reidy D, Thawer A, Whitman J, Wu L, Singh S. Temozolomide in grade III neuroendocrine neoplasms (G3 NENs): A multicenter retrospective review. Journal Of Clinical Oncology 2019, 37: 321-321. DOI: 10.1200/jco.2019.37.4_suppl.321.Peer-Reviewed Original ResearchTreatment failureG3 NENRetrospective reviewDose reduction/discontinuationBest radiological responseLocal pathology reportsMulticentre retrospective reviewOptimal systemic treatmentProspective confirmatory trialMedian TTFMulticenter retrospective reviewReduction/discontinuationBetter response rateViable treatment optionGastroenteropancreatic NENRadiologic responseStable diseasePrimary endpointRECIST criteriaAdverse eventsOverall survivalPartial responseProgressive diseaseRadiological responseSystemic treatment
2018
Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial
Pavel M, Gross DJ, Benavent M, Perros P, Srirajaskanthan R, Warner RRP, Kulke MH, Anthony LB, Kunz PL, Hörsch D, Weickert MO, Lapuerta P, Jiang W, Kassler-Taub K, Wason S, Fleming R, Fleming D, Garcia-Carbonero R. Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial. Endocrine Related Cancer 2018, 25: 309-322. PMID: 29330194, PMCID: PMC5811631, DOI: 10.1530/erc-17-0455.Peer-Reviewed Original ResearchConceptsTreatment-emergent adverse eventsOpen-label extensionCarcinoid syndromeTelotristat ethylSomatostatin analoguesWeek 12Rates of TEAEsDouble-blind treatment periodPhase 3 trialTryptophan hydroxylase inhibitorMedian treatment differencesCS diarrheaBowel movementsEfficacy endpointAdverse eventsPrimary safetyTreatment periodHydroxylase inhibitorPatientsSerious eventsPercent changeTreatment differencesPlaceboEfficacySignificant reduction
2017
Association of weight change with telotristat ethyl in the treatment of carcinoid syndrome.
Weickert M, Kaltsas G, Hörsch D, Lapuerta P, Pavel M, Valle J, Caplin M, Bergsland E, Kunz P, Anthony L, Grande E, Oberg K, Warner R, Lombard-Bohas C, Welin S, Fleming R, Kittur A, Arnold K, Yang Q, Kulke M. Association of weight change with telotristat ethyl in the treatment of carcinoid syndrome. Journal Of Clinical Oncology 2017, 35: e15692-e15692. DOI: 10.1200/jco.2017.35.15_suppl.e15692.Peer-Reviewed Original ResearchMetastatic neuroendocrine tumorsCarcinoid syndromeWeek 12Neuroendocrine tumorsTelotristat ethylWeight gainWeight lossWeight changeDouble-blind treatment periodUncontrolled carcinoid syndromeBowel movement frequencyBody mass indexCochrane-Armitage testStatistical analysis planBM frequencyAdverse eventsAnalogue therapyDiarrhea severityPerformance statusMass indexBaseline ageTreatment periodPatientsReduced survivalIncidence
2013
Phase II Study Evaluating 2 Dosing Schedules of Oral Foretinib (GSK1363089), cMET/VEGFR2 Inhibitor, in Patients with Metastatic Gastric Cancer
Shah MA, Wainberg ZA, Catenacci DV, Hochster HS, Ford J, Kunz P, Lee FC, Kallender H, Cecchi F, Rabe DC, Keer H, Martin AM, Liu Y, Gagnon R, Bonate P, Liu L, Gilmer T, Bottaro DP. Phase II Study Evaluating 2 Dosing Schedules of Oral Foretinib (GSK1363089), cMET/VEGFR2 Inhibitor, in Patients with Metastatic Gastric Cancer. PLOS ONE 2013, 8: e54014. PMID: 23516391, PMCID: PMC3597709, DOI: 10.1371/journal.pone.0054014.Peer-Reviewed Original ResearchConceptsObjective response rateMetastatic gastric cancerStable diseaseMET amplificationPhospho-METGastric adenocarcinomaIntermittent dosingGastric cancerTreatment-related adverse eventsPhase II studyMetastatic gastric adenocarcinomaRates of hypertensionElevated aspartate aminotransferaseOral multikinase inhibitorEndothelial cell growth factorVascular endothelial cell growth factorCell growth factorEvaluable patientsForetinib treatmentPrior therapyAdverse eventsII studyUnselected patientsDosing schedulesMedian age
2009
Assessment of two dosing schedules of GSK1363089 (GSK089), a dual MET/VEGFR2 inhibitor, in metastatic gastric cancer (GC): Interim results of a multicenter phase II study
Jhawer M, Kindler H, Wainberg Z, Ford J, Kunz P, Tang L, McCallum S, Kallender H, Shah M. Assessment of two dosing schedules of GSK1363089 (GSK089), a dual MET/VEGFR2 inhibitor, in metastatic gastric cancer (GC): Interim results of a multicenter phase II study. Journal Of Clinical Oncology 2009, 27: 4502-4502. DOI: 10.1200/jco.2009.27.15_suppl.4502.Peer-Reviewed Original ResearchMetastatic gastric cancerPhase II studyGastric cancerStable diseaseAdverse eventsCMET amplificationEvaluable ptsII studyDosing schedulesGrade 5 adverse eventsMulticenter phase II studyAdequate organ functionECOG PS 0Prior chemotherapy regimensTreatment tumor biopsiesAntitumor activityDaily dosing schedulePrimary study endpointMinimal antitumor activityAttractive therapeutic targetCMET pathwayLFT abnormalitiesMeasurable diseaseTreatment biopsiesChemotherapy regimens