2024
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.
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
2020
Patient Selection and Toxicities of PRRT for Metastatic Neuroendocrine Tumors and Research Opportunities
Shaheen S, Moradi F, Gamino G, Kunz PL. Patient Selection and Toxicities of PRRT for Metastatic Neuroendocrine Tumors and Research Opportunities. Current Treatment Options In Oncology 2020, 21: 25. PMID: 32172368, DOI: 10.1007/s11864-020-0711-9.Peer-Reviewed Original ResearchConceptsPeptide receptor radionuclide therapySomatostatin analoguesToxicity of PRRTOpinion statementNeuroendocrine tumorsMetastatic neuroendocrine tumorsLandscape of treatmentReceptor radionuclide therapyRecent treatment advancesTreatment of NETsPatient selectionNeuroendocrine tumorsTreatment advancesSomatostatin receptorsMinimal response rateRadionuclide therapyResponse rateHeterogenous groupTherapyTumor cellsBiological hallmarksTumorsTreatmentNETsIndolentNeoplasmsTime to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl: Analyses of Phase III Studies in Carcinoid Syndrome
Dillon JS, Kulke MH, Hörsch D, Anthony LB, Warner RRP, Bergsland E, Welin S, O’Dorisio T, Kunz PL, McKee C, Lapuerta P, Banks P, Pavel M. Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl: Analyses of Phase III Studies in Carcinoid Syndrome. Journal Of Gastrointestinal Cancer 2020, 52: 212-221. PMID: 32146619, PMCID: PMC7714089, DOI: 10.1007/s12029-020-00375-2.Peer-Reviewed Original ResearchConceptsCarcinoid syndrome diarrheaBM frequencyPhase III studyTelotristat ethylBowel movementsCarcinoid syndromeIII studySomatostatin analoguesDouble-blind treatment periodBowel movement frequencyMajority of patientsLog-rank testCox regression modelTime of onsetPlacebo TIDHazard ratioPrespecified analysisMedian timeSustained responseTreatment periodSustained reductionPatientsConsecutive weeksTELESTARSurvival analysis methods
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
Efficacy and safety of telotristat ethyl in patients with carcinoid syndrome inadequately controlled by somatostatin analogs: Analysis of the completed TELESTAR extension period
Horsch D, Kulke M, Caplin M, Anthony L, Bergsland E, Oberg K, Warner R, Kunz P, Pulido E, Valle J, Dillon J, Lapuerta P, Banks P, Jackson S, Pavel M. Efficacy and safety of telotristat ethyl in patients with carcinoid syndrome inadequately controlled by somatostatin analogs: Analysis of the completed TELESTAR extension period. Endocrine Abstracts 2017 DOI: 10.1530/endoabs.52.p14.Peer-Reviewed Original Research440PD Efficacy and safety of telotristat ethyl in patients with carcinoid syndrome inadequately controlled by somatostatin analogs: Analysis of the completed TELESTAR extension period
Hörsch D, Kulke M, Caplin M, Anthony L, Bergsland E, Öberg K, Warner R, Kunz P, Pulido E, Valle J, Dillon J, Lapuerta P, Banks P, Jackson S, Pavel M. 440PD Efficacy and safety of telotristat ethyl in patients with carcinoid syndrome inadequately controlled by somatostatin analogs: Analysis of the completed TELESTAR extension period. Annals Of Oncology 2017, 28: v147. DOI: 10.1093/annonc/mdx368.012.Peer-Reviewed Original Research
2016
Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome
Kulke MH, Hörsch D, Caplin ME, Anthony LB, Bergsland E, Öberg K, Welin S, Warner RR, Lombard-Bohas C, Kunz PL, Grande E, Valle JW, Fleming D, Lapuerta P, Banks P, Jackson S, Zambrowicz B, Sands AT, Pavel M. Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome. Journal Of Clinical Oncology 2016, 35: 14-23. PMID: 27918724, DOI: 10.1200/jco.2016.69.2780.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Agents, HormonalDefecationDiarrheaDouble-Blind MethodFemaleGamma-GlutamyltransferaseGastrointestinal AgentsHumansHydroxyindoleacetic AcidMaleMalignant Carcinoid SyndromeMiddle AgedNauseaOctreotidePeptides, CyclicPhenylalaninePyrimidinesSomatostatinTryptophan HydroxylaseConceptsDouble-blind treatment periodOpen-label extensionTelotristat ethylTryptophan hydroxylase inhibitorBM frequencyCarcinoid syndromeWeek 12Treatment periodHydroxylase inhibitorPlacebo-controlled phase III studyPrimary end pointSomatostatin analogue therapyBowel movement frequencyNew safety signalsPhase III studyGamma-glutamyl transferaseAsymptomatic increaseMild nauseaAnalogue therapyIII studyMethods PatientsSomatostatin analoguesSafety signalsPlaceboPatientsRole of Somatostatin Analogues in the Treatment of Neuroendocrine Tumors
Narayanan S, Kunz PL. Role of Somatostatin Analogues in the Treatment of Neuroendocrine Tumors. Hematology/Oncology Clinics Of North America 2016, 30: 163-177. PMID: 26614375, DOI: 10.1016/j.hoc.2015.09.008.Peer-Reviewed Original ResearchConceptsSomatostatin analoguesNeuroendocrine tumorsRole of SSAsTreatment of NETsPeptide receptor radionuclide therapyMetastatic neuroendocrine tumorsHormone-related symptomsReceptor radionuclide therapyRare epithelial neoplasmLocal therapySymptom managementTumor controlNeuroendocrine differentiationEffective therapyEpithelial neoplasmsDisease CenterPromising treatmentRadionuclide therapyTumor growthTherapyTreatmentTumorsSurgeryNeoplasmsLung
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 therapyRole of somatostatin analogues in the treatment of neuroendocrine tumors.
Narayanan S, Kunz PL. Role of somatostatin analogues in the treatment of neuroendocrine tumors. Journal Of The National Comprehensive Cancer Network 2015, 13: 109-17; quiz 117. PMID: 25583773, DOI: 10.6004/jnccn.2015.0012.Peer-Reviewed Original ResearchConceptsNeuroendocrine tumorsSomatostatin analoguesTumor controlTreatment of NETsSystemic tumor controlHormone-related symptomsManagement of patientsRare epithelial neoplasmAdvanced diseaseHormone excessSymptom managementNeuroendocrine differentiationEpithelial neoplasmsGastrointestinal tractPatientsTumorsTreatmentDiarrheaNeoplasmsLungSerotoninSyndromeSymptomsManagementMainstay
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 treatmentPhase II clinical trial of pasireotide LAR in patients with metastatic neuroendocrine tumors.
Strosberg J, Jump H, Valone T, Weber J, Khandelwal V, Kunz P. Phase II clinical trial of pasireotide LAR in patients with metastatic neuroendocrine tumors. Journal Of Clinical Oncology 2014, 32: 241-241. DOI: 10.1200/jco.2014.32.3_suppl.241.Peer-Reviewed Original ResearchPasireotide LARSomatostatin analoguesMedian PFSLong-term insulin therapySomatostatin receptor subtypes 1Phase II clinical trialBest radiographic responseGrade 3 hyperglycemiaPrior systemic therapyRates of hyperglycemiaYear OS ratesTreatment-naïve patientsMetastatic neuroendocrine tumorsPhase II trialIntermediate-grade tumorsNovel somatostatin analogReceptor subtype 1LAR treatmentQ4 weeksStable diseaseII trialNaïve patientsPrimary endpointRefractory patientsInsulin therapy
2012
A renaissance in therapeutic options for pancreatic neuroendocrine tumors.
Kunz PL. A renaissance in therapeutic options for pancreatic neuroendocrine tumors. American Society Of Clinical Oncology Educational Book 2012, 271-4. PMID: 24451747, DOI: 10.14694/edbook_am.2012.32.136.Peer-Reviewed Original ResearchProgression-free survivalPancreatic neuroendocrine tumorsNeuroendocrine tumorsTherapeutic optionsRandomized placebo-controlled studyPlacebo-controlled studyNovel therapeutic optionsChemotherapy backboneLocoregional diseaseAdvanced diseaseBiologic therapySurgical resectionSomatostatin analoguesClinical trialsDrug AdministrationU.S. FoodAntiproliferative agentsTumorsDiseaseFuture studiesResectionEverolimusSunitinibPatientsOptions
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