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 careSafety 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 abnormalities[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
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 trialFinal overall survival in the phase 3 NETTER-1 study of lutetium-177-DOTATATE in patients with midgut neuroendocrine tumors.
Strosberg J, Caplin M, Kunz P, Ruszniewski P, Bodei L, Hendifar A, Mittra E, Wolin E, Yao J, Pavel M, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Demange A, Mutevelic S, Krenning E, group O. Final overall survival in the phase 3 NETTER-1 study of lutetium-177-DOTATATE in patients with midgut neuroendocrine tumors. Journal Of Clinical Oncology 2021, 39: 4112-4112. DOI: 10.1200/jco.2021.39.15_suppl.4112.Peer-Reviewed Original ResearchProgression-free survivalMedian overall survivalFinal overall survivalNETTER-1 studyNETTER-1 trialNew safety signalsOverall survivalMidgut neuroendocrine tumorsControl armMyelodysplastic syndromeNeuroendocrine tumorsLu-DOTATATEPrimary endpointLast patientSafety signalsFurther anti-cancer treatmentBest supportive careKey secondary endpointOpen-label trialLutetium-177 DOTATATEAnti-cancer treatmentEligible patientsNETTER-1RECIST 1.1Secondary endpoints
2018
Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With 177Lu-Dotatate in the Phase III NETTER-1 Trial
Strosberg J, Wolin E, Chasen B, Kulke M, Bushnell D, Caplin M, Baum RP, Kunz P, Hobday T, Hendifar A, Oberg K, Sierra ML, Thevenet T, Margalet I, Ruszniewski P, Krenning E, Group O. Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With 177Lu-Dotatate in the Phase III NETTER-1 Trial. Journal Of Clinical Oncology 2018, 36: jco.2018.78.586. PMID: 29878866, PMCID: PMC6366953, DOI: 10.1200/jco.2018.78.5865.Peer-Reviewed Original ResearchConceptsNETTER-1 trialPhase III studyGlobal health statusHealth-related QoL.Quality of lifeMidgut NETQoL deteriorationIII studyLu-DOTATATEPhysical functioningHealth statusEuropean OrganizationTumor progressionInternational phase III studyDisease-related worriesSignificant QOL benefitsProgression-free survivalMidgut neuroendocrine tumorsNeuroendocrine tumor progressionImpact of treatmentLu-DOTATATE treatmentTreat populationQLQ CCancer QualityQOL scores
2017
The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors
Strosberg JR, Halfdanarson TR, Bellizzi AM, Chan JA, Dillon JS, Heaney AP, Kunz PL, O’Dorisio T, Salem R, Segelov E, Howe JR, Pommier RF, Brendtro K, Bashir MA, Singh S, Soulen MC, Tang L, Zacks JS, Yao JC, Bergsland EK. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors. Pancreas 2017, 46: 707-714. PMID: 28609356, PMCID: PMC5642985, DOI: 10.1097/mpa.0000000000000850.Peer-Reviewed Original ResearchConceptsMidgut neuroendocrine tumorsNeuroendocrine tumorsNorth American Neuroendocrine Tumor Society Consensus GuidelinesNorth American Neuroendocrine Tumor SocietyNETTER-1 trialRADIANT-4 studyRefractory carcinoid syndromePhase 3 studyNonfunctioning neuroendocrine tumorEnteropancreatic neuroendocrine tumorsConsensus-based guidelinesCLARINET trialRADIANT-2Carcinoid syndromeTelotristat ethylMedical managementTherapeutic optionsConsensus guidelinesSurgical guidelinesLu-DOTATATEMultidisciplinary panelProximal colonGastrointestinal tractSmall intestinePatientsQuality-of-life findings in patients with midgut neuroendocrine tumors: Results of the NETTER-1 phase III trial.
Strosberg J, Wolin E, Chasen B, Kulke M, Bushnell D, Caplin M, Baum R, Kunz P, Hobday T, Hendifar A, Oberg K, Lopera Sierra M, Kwekkeboom D, Ruszniewski P, Krenning E. Quality-of-life findings in patients with midgut neuroendocrine tumors: Results of the NETTER-1 phase III trial. Journal Of Clinical Oncology 2017, 35: 348-348. DOI: 10.1200/jco.2017.35.4_suppl.348.Peer-Reviewed Original ResearchGlobal health statusMidgut NETHealth statusHigh-dose octreotide LARNETTER-1 trialPhase III trialsProgression-free survivalEORTC QLQ-30Health-related qualityHormone-related symptomsMidgut neuroendocrine tumorsNeuroendocrine tumor progressionImpact of treatmentQuality of lifeOctreotide LARIII trialsQLQ-30Patients' QoLNeuroendocrine tumorsQOL analysisLu-DOTATATEDisease progressionLife findingsPatientsBaseline scoresPhase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors
Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. New England Journal Of Medicine 2017, 376: 125-135. PMID: 28076709, PMCID: PMC5895095, DOI: 10.1056/nejmoa1607427.Peer-Reviewed Original ResearchConceptsMidgut neuroendocrine tumorsProgression-free survivalAdvanced midgut neuroendocrine tumorsOverall survivalNeuroendocrine tumorsControl groupInterim analysisResponse rateLu-DOTATATEHigh-dose octreotide LARLonger progression-free survivalEnd pointMetastatic midgut neuroendocrine tumorsFinal analysisData cutoff dateObjective response rateOverall survival benefitPrimary end pointSecondary end pointsSomatostatin analogue therapyPhase 3 trialSide effect profileRenal toxic effectsHigh response rateOctreotide LAR
2016
NETTER-1 phase III: Efficacy and safety results in patients with midgut neuroendocrine tumors treated with 177 Lu-DOTATATE.
Strosberg J, Wolin E, Chasen B, Kulke M, Bushnell D, Caplin M, Baum R, Hobday T, Hendifar A, Oberg K, Lopera Sierra M, Kwekkeboom D, Ruszniewski P, Krenning E, Kunz P. NETTER-1 phase III: Efficacy and safety results in patients with midgut neuroendocrine tumors treated with 177 Lu-DOTATATE. Journal Of Clinical Oncology 2016, 34: 4005-4005. DOI: 10.1200/jco.2016.34.15_suppl.4005.Peer-Reviewed Original Research