2020
Time 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
Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome
Weickert MO, Kaltsas G, Hörsch D, Lapuerta P, Pavel M, Valle JW, Caplin ME, Bergsland E, Kunz PL, Anthony LB, Grande E, Öberg K, Welin S, Lombard-Bohas C, Ramage JK, Kittur A, Yang QM, Kulke MH. Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome. Clinical Therapeutics 2018, 40: 952-962.e2. PMID: 29724499, DOI: 10.1016/j.clinthera.2018.04.006.Peer-Reviewed Original ResearchConceptsMetastatic neuroendocrine tumorsTelotristat ethylCarcinoid syndromePlacebo TIDWeek 12Neuroendocrine tumorsMetabolic parametersNutritional statusDouble-blind treatment periodWeight gainWeight lossUncontrolled carcinoid syndromeSomatostatin analogue therapyBowel movement frequencyStatistical analysis planOverall nutritional statusAnalogue therapyDiarrhea severityTreatment periodPatientsSyndromeWeight changeAnalysis planMovement frequencyTumorsTelotristat 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 ResearchUnderstanding the Patient Experience with Carcinoid Syndrome: Exit Interviews from a Randomized, Placebo-controlled Study of Telotristat Ethyl
Anthony L, Ervin C, Lapuerta P, Kulke MH, Kunz P, Bergsland E, Hörsch D, Metz DC, Pasieka J, Pavlakis N, Pavel M, Caplin M, Öberg K, Ramage J, Evans E, Yang QM, Jackson S, Arnold K, Law L, DiBenedetti DB. Understanding the Patient Experience with Carcinoid Syndrome: Exit Interviews from a Randomized, Placebo-controlled Study of Telotristat Ethyl. Clinical Therapeutics 2017, 39: 2158-2168. PMID: 29074312, DOI: 10.1016/j.clinthera.2017.09.013.Peer-Reviewed Original ResearchConceptsTelotristat ethylBM frequencyCarcinoid syndromeBowel movementsPatient experienceDouble-blind treatment periodCarcinoid syndrome symptomsPrimary end pointSomatostatin analogue therapyPhase III studyClinical trial experienceTryptophan hydroxylase inhibitorEligible patientsStudy drugAnalogue therapyIII studyPatient interviewsResponder analysisTreatment periodPatient reportsSyndrome symptomsTreatment responsePrespecified criteriaHydroxylase inhibitorPatients440PD 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 ResearchThe 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 intestinePatientsAssociation 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
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 signalsPlaceboPatients422PD Integrated placebo-controlled safety analysis from clinical studies of telotristat ethyl for the treatment of carcinoid syndrome
Kulke M, Hörsch D, Caplin M, Anthony L, Bergsland E, Oberg K, Welin S, Warner R, Bohas C, Kunz P, Grande E, Valle J, Lapuerta P, Banks P, Jackson S, Jiang W, Biran T, Pavel M. 422PD Integrated placebo-controlled safety analysis from clinical studies of telotristat ethyl for the treatment of carcinoid syndrome. Annals Of Oncology 2016, 27: vi138. DOI: 10.1093/annonc/mdw369.07.Peer-Reviewed Original Research