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 care[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
2022
Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211)
Kunz PL, Graham NT, Catalano PJ, Nimeiri HS, Fisher GA, Longacre TA, Suarez CJ, Martin BA, Yao JC, Kulke MH, Hendifar AE, Shanks JC, Shah MH, Zalupski MM, Schmulbach EL, Reidy-Lagunes DL, Strosberg JR, O'Dwyer PJ, O'Dwyer P, Benson A. Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211). Journal Of Clinical Oncology 2022, 41: 1359-1369. PMID: 36260828, PMCID: PMC9995105, DOI: 10.1200/jco.22.01013.Peer-Reviewed Original ResearchConceptsAdvanced pancreatic neuroendocrine tumorsProgression-free survivalPancreatic neuroendocrine tumorsMedian progression-free survivalPrimary end pointNeuroendocrine tumorsResponse rateObjective responseOverall survivalRandomized studyIntermediate-grade pancreatic neuroendocrine tumorsLonger progression-free survivalEnd pointMGMT deficiencyMedian overall survivalPrimary analysis populationKey eligibility criteriaPhase II trialSmall prospective studiesHigh response rateMethylguanine methyltransferaseCapecitabine/Eligible patientsSecondary endpointsII trialA randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: Final analysis of efficacy and evaluation of MGMT (ECOG-ACRIN E2211).
Kunz P, Graham N, Catalano P, Nimeiri H, Fisher G, Longacre T, Suarez C, Rubin D, Yao J, Kulke M, Hendifar A, Shanks J, Shah M, Zalupski M, Schmulbach E, Reidy D, Strosberg J, Wong T, O'Dwyer P, Benson A. A randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: Final analysis of efficacy and evaluation of MGMT (ECOG-ACRIN E2211). Journal Of Clinical Oncology 2022, 40: 4004-4004. DOI: 10.1200/jco.2022.40.16_suppl.4004.Peer-Reviewed Original ResearchProgression-free survivalPancreatic neuroendocrine tumorsMedian progression-free survivalAdvanced pancreatic neuroendocrine tumorsCombination of capecitabineNeuroendocrine tumorsResponse rateEligible patientsPrimary endpointOverall survivalIntermediate-grade pancreatic neuroendocrine tumorsTwo-sided log-rank testLonger progression-free survivalEfficacy analysis populationObjective tumor responsePhase II trialLog-rank testHigh response rateSecondary endpointsII trialProspective studyAnalysis populationTreatment optionsTumor responseInterim analysis
2021
Rapid Progression After 177Lu-DOTATATE in Patients With Neuroendocrine Tumors
Assi HA, Hornbacker K, Shaheen S, Wittenberg T, Silberman R, Kunz PL. Rapid Progression After 177Lu-DOTATATE in Patients With Neuroendocrine Tumors. Pancreas 2021, 50: 890-894. PMID: 34398071, DOI: 10.1097/mpa.0000000000001841.Peer-Reviewed Original ResearchConceptsPeptide receptor radionuclide therapyProgressive diseaseNeuroendocrine tumorsBiopsy-proven neuroendocrine tumorHigher disease control rateMedian progression-free survivalShorter progression-free intervalStanford Cancer CenterDisease control rateMetastatic neuroendocrine tumorsMonths of therapyProgression-free survivalProgression-free intervalReceptor radionuclide therapyBetter patient selectionLarge patient cohortHigh-grade componentHigher disease gradeLow-grade componentRepeat biopsyMedian timePatient selectionInitial pathologyPredictive factorsCancer Center
2020
Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study
Strosberg J, Kunz PL, Hendifar A, Yao J, Bushnell D, Kulke MH, Baum RP, Caplin M, Ruszniewski P, Delpassand E, Hobday T, Verslype C, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Paganelli G, Severi S, Morse M, Metz DC, Ansquer C, Courbon F, Al-Nahhas A, Baudin E, Giammarile F, Taïeb D, Mittra E, Wolin E, O’Dorisio T, Lebtahi R, Deroose CM, Grana CM, Bodei L, Öberg K, Polack BD, He B, Mariani MF, Gericke G, Santoro P, Erion JL, Ravasi L, Krenning E. Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study. European Journal Of Nuclear Medicine And Molecular Imaging 2020, 47: 2372-2382. PMID: 32123969, PMCID: PMC7396396, DOI: 10.1007/s00259-020-04709-x.Peer-Reviewed Original ResearchConceptsLiver tumor burdenProgression-free survivalLargest target lesionHigher liver tumour burdenTumor burdenMidgut neuroendocrine tumorsAlkaline phosphatase elevationNeuroendocrine tumorsTarget lesionsLesion sizeHazard ratioTreatment outcomesAnalysis of PFSHigh-dose octreotide LARMedian progression-free survivalImproved progression-free survivalNETTER-1 studyNETTER-1 trialLiver function abnormalitiesKaplan-Meier estimatesOctreotide LARPrimary endpointFunction abnormalitiesBaseline factorsCox regression
2014
Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors
Cives M, Kunz P, Morse B, Coppola D, Schell M, Campos T, Nguyen P, Nandoskar P, Khandelwal V, Strosberg J. Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors. Endocrine Related Cancer 2014, 22: 1-9. PMID: 25376618, PMCID: PMC4643672, DOI: 10.1530/erc-14-0360.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall radiographic response rateOverall survivalPasireotide LARSomatostatin analoguesFirst-line systemic agentMedian progression-free survivalPhase II clinical trialGrade 3 hyperglycemiaMetastatic grade 1Neuroendocrine tumor growthPrevious systemic therapyRadiographic response rateRates of hyperglycemiaGrade 3/4 toxicitiesMedian overall survivalMetastatic neuroendocrine tumorsPhase II studySolid Tumors criteriaTreatment-naïve patientsHepatic tumor burdenResponse Evaluation CriteriaNovel somatostatin analogReceptor subtype 1LAR treatmentA phase II study of capecitabine, carboplatin, and bevacizumab for metastatic or unresectable gastroesophageal junction and gastric adenocarcinoma.
Kunz P, Nandoskar P, Koontz M, Ji H, Ford J, Balise R, Kamaya A, Rubin D, Fisher G. A phase II study of capecitabine, carboplatin, and bevacizumab for metastatic or unresectable gastroesophageal junction and gastric adenocarcinoma. Journal Of Clinical Oncology 2014, 32: 115-115. DOI: 10.1200/jco.2014.32.3_suppl.115.Peer-Reviewed Original ResearchProgression-free survivalGastroesophageal junctionStable diseaseOverall survivalPartial responseGastric adenocarcinomaPrimary endpointProgressive diseaseDay 1Response rateMedian progression-free survivalCombination of capecitabineFirst tumor assessmentBest supportive careMedian overall survivalPhase II studyPromising response ratesAddition of bevacizumabIncidence of adenocarcinomaMajor health problemQuality of lifeSecondary endpointsBaseline characteristicsFree survivalGastric cardia