2024
[177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high‑dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2–3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study
Singh S, Halperin D, Myrehaug S, Herrmann K, Pavel M, Kunz P, Chasen B, Tafuto S, Lastoria S, Capdevila J, García-Burillo A, Oh D, Yoo C, Halfdanarson T, Falk S, Folitar I, Zhang Y, Aimone P, de Herder W, Ferone D, Investigators A. [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high‑dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2–3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study. The Lancet 2024, 403: 2807-2817. PMID: 38851203, DOI: 10.1016/s0140-6736(24)00701-3.Peer-Reviewed Original ResearchGastroenteropancreatic neuroendocrine tumorsProgression-free survivalAdvanced gastroenteropancreatic neuroendocrine tumorsLong-acting octreotideLu-DOTATATENeuroendocrine tumorsGrade 2Open-labelControl groupTreated patientsWell-differentiatedStandard first-line treatment optionMedian progression-free survivalProgression-free survival eventsTreatment periodFirst-line treatment optionProgression-free survival analysisNeuroendocrine tumor gradingSomatostatin receptor-positiveFirst-line therapyInteractive response technologyHigh-dose octreotidePhase 3 studyPhase 3 trialStandard of care211MO First-line efficacy of [177Lu]Lu-DOTA-TATE in patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors by tumor grade and primary origin: Subgroup analysis of the phase III NETTER-2 study
Singh S, Halperin D, Myrehaug S, Herrmann K, Pavel M, Kunz P, Chasen B, Capdevila J, Tafuto S, Oh D, Yoo C, Falk S, Halfdanarson T, Folitar I, Zhang Y, de Herder W, Ferone D. 211MO First-line efficacy of [177Lu]Lu-DOTA-TATE in patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors by tumor grade and primary origin: Subgroup analysis of the phase III NETTER-2 study. Annals Of Oncology 2024, 35: s92-s93. DOI: 10.1016/j.annonc.2024.05.219.Peer-Reviewed Original ResearchFirst-line efficacyGastroenteropancreatic neuroendocrine tumorsNeuroendocrine tumorsTumor gradeGrade 3Subgroup analysisGrade 2TumorPrimary originSafety 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[177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Primary analysis of the phase 3 randomized NETTER-2 study
Ferone D, Halperin D, Myrehaug S, Herrmann K, Pavel M, Kunz P, Chasen B, Capdevila J, Tafuto S, Oh D, Yoo C, Falk S, Halfdanarson T, Folitar I, Zhang Y, Santoro P, Aimone P, de H, Singh S. [177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Primary analysis of the phase 3 randomized NETTER-2 study. Endocrine Abstracts 2024 DOI: 10.1530/endoabs.99.oc7.2.Peer-Reviewed Original ResearchGastroenteropancreatic neuroendocrine tumorsNeuroendocrine tumorsGrade 3Diagnosed patientsGrade 2Primary analysis[177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Primary analysis of the phase 3 randomized NETTER-2 study.
Singh S, Halperin D, Myrehaug S, Herrmann K, Pavel M, Kunz P, Chasen B, Capdevila J, Tafuto S, Oh D, Yoo C, Falk S, Halfdanarson T, Folitar I, Zhang Y, Santoro P, Aimone P, de Herder W, Ferone D. [177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Primary analysis of the phase 3 randomized NETTER-2 study. Journal Of Clinical Oncology 2024, 42: lba588-lba588. DOI: 10.1200/jco.2024.42.3_suppl.lba588.Peer-Reviewed Original ResearchProgression-free survivalObjective response rateOctreotide long-acting releaseLong-acting releaseGastroenteropancreatic neuroendocrine tumorsRadioligand therapyGEP-NETsLu-DOTATATENeuroendocrine tumorsControl armEfficacy of radioligand therapyMedian progression-free survivalProlonged progression-free survivalCases of myelodysplastic syndromeAdvanced GEP-NETsMedian cumulative doseStratified hazard ratioStratified odds ratiosMonths prior to enrollmentLu-DOTATATE treatmentUnmet medical needG3 tumorsMyelodysplastic syndromePrognostic subgroupsEligible pts
2023
1198P 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
Strosberg J, Ulaner G, Halperin D, Mehr S, Li D, Soares H, Anthony L, Kotiah S, Jacene H, Kunz P, Ferreira D, Li J, Ma K, Rearden J, Moran S, Hope T, Singh S, Morris M. 1198P 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. Annals Of Oncology 2023, 34: s707. DOI: 10.1016/j.annonc.2023.09.731.Peer-Reviewed Original ResearchPhase Ib portionSomatostatin analogue therapyGastroenteropancreatic neuroendocrine tumorsAnalogue therapyEfficacy findingsNeuroendocrine tumorsTherapyTumorsTrialsACTION-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
92: [177Lu]Lu-Dota-Tate as First-Line Therapy for Patients with Grade 2 and 3 Advanced Gastroenteropancreatic Neuroendocrine Tumours (GEP-NETS): The NETTER-2 Study
Myrehaug S, Singh S, Pavel M, Kunz P, de Herder W, Herrmann K, D’Amelio A, Santoro P, Folitar I, Ferone D. 92: [177Lu]Lu-Dota-Tate as First-Line Therapy for Patients with Grade 2 and 3 Advanced Gastroenteropancreatic Neuroendocrine Tumours (GEP-NETS): The NETTER-2 Study. Radiotherapy And Oncology 2022, 174: s40-s41. DOI: 10.1016/s0167-8140(22)04371-7.Peer-Reviewed Original ResearchAdvanced gastroenteropancreatic neuroendocrine tumorsGastroenteropancreatic neuroendocrine tumorsLine therapyNeuroendocrine tumorsGrade 2DOTA-TATEPatientsTherapyTumors
2020
Evaluation of the incidence of acute nausea and vomiting after administration of an amino acid solution containing only arginine and lysine with lutetium Lu-177 dotatate.
Alonzo N, Seyer M, Kim E, Keshavarzi R, Yee K, Kunz P. Evaluation of the incidence of acute nausea and vomiting after administration of an amino acid solution containing only arginine and lysine with lutetium Lu-177 dotatate. Journal Of Clinical Oncology 2020, 38: 12113-12113. DOI: 10.1200/jco.2020.38.15_suppl.12113.Peer-Reviewed Original ResearchLu-177 DOTATATEAA infusionAmino acid solutionRates of nauseaPercentage of patientsRetrospective chart reviewGastroenteropancreatic neuroendocrine tumorsAcute nauseaSecondary endpointsAdult patientsChart reviewNeuroendocrine tumorsNormal salinePatientsInfusion timeAA solutionIncidenceDOTATATEInfusionHistorical incidenceAmino acids 10NauseaVomitingAdministrationEssential AA
2015
New and Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors.
Phan AT, Kunz PL, Reidy-Lagunes DL. New and Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors. Clinical Advances In Hematology And Oncology 2015, 13: 1-18; quiz 1 p following 18. PMID: 26430956.Peer-Reviewed Original ResearchConceptsGastroenteropancreatic neuroendocrine tumorsGEP-NETsSomatostatin analoguesTreatment optionsNeuroendocrine tumorsPancreatic NETsLanreotide depot/autogelClassical carcinoid syndromeExtent of metastasisFirst-line treatmentHepatic arterial embolizationMetastatic carcinoid tumorsValvular heart diseasePrimary tumor siteComplex of symptomsAgents everolimusUnresectable diseaseCarcinoid syndromeCytoreductive surgeryArterial embolizationLiver metastasesPalliative treatmentCarcinoid tumorsClinical symptomsAblative therapy
2010
Advances in the treatment of gastroenteropancreatic neuroendocrine tumors
Kunz PL, Fisher GA. Advances in the treatment of gastroenteropancreatic neuroendocrine tumors. Clinical And Experimental Gastroenterology 2010, Volume 3: 79-86. PMID: 21694850, PMCID: PMC3108662, DOI: 10.2147/ceg.s5928.Peer-Reviewed Original ResearchGastroenteropancreatic neuroendocrine tumorsSomatostatin analoguesNeuroendocrine tumorsTumor growthExcellent performance statusMainstay of treatmentNon-surgical therapyEnd-organ effectsExternal beam radiationNovel therapeutic trialsTyrosine kinase inhibitorsEarly promising resultsSecretion of peptidesSystemic chemotherapyLocoregional therapyPerformance statusMetastatic diseaseStandard chemotherapySurgical resectionMedical therapyTherapeutic trialsGEP-NETsTumor massMTOR inhibitorsAngiogenesis inhibitors