Die RamuNET Studie (offene Phase II AIO assoziierte Studie mit Ramucirumab und Dacarbazin bei progredienten pankreatischen NET) (LKP Prof. Michl, Uniklinikum Heidelberg) sowie die CABONEN Studie (offene Phase 2 Studie mit Cabozantinib bei Patienten mit fortgeschrittenen, NET G3 und low grade NEC mit bis zu 60% Proliferationsrate (CABONEN; LKP PD Dr. A. König, Uniklinikum Göttingen) wurden 2024 auf dem ESMO präsentiert und befinden sich nun in der finalen Vorbereitung für eine Publikation, die in diesem Jahr noch eingereicht werden sollen.

Die COMPETE Studie (internationale randomisierte Phase 3 Studie, PRRT mit 177Lu-Edotreotid vs. Everolimus in GEP-NET, LKP Prof. Baum, Wiesbaden) beendet bereits in 2023 die Rekrutierung und eine erste Analyse wurde auf dem ENETS 2025 in Krakau präsentiert sowie neuere Subgruppenanalysen auf dem ESMO 2025.

Innerhalb des Kalenderjahres 2025 wurden zwei außerplanmäßig AG NET Sitzungen am 09.07.2025 und am 24.09.2025 organisiert. Über die AIO erfolgte die Einladung. Geplant ist ein regelmäßiger Austausch neben den gesetzten AIO Frühjahrs- und Herbsttagungen alle 2-3 Monate. Dabei wurden Studienideen intensiv diskutiert und dezidiert weitere Schritte inklusive Arbeitsaufteilung besprochen. Ein neues Projekt ist die Gründung der „Rare NET Initiative“ unter der Federführung von Sabrina Sulzer (Göttingen) und Leonidas Apostolidis (Heidelberg). Dabei sollen seltene Neuroendokrine Neoplasien (z.B. NET des Ovars) hinsichtlich ihres Tumor-biologischen Verhaltens, Diagnostik und Therapie strukturiert aufgearbeitet werden. Ein breites Ethikvotum ist in Planung und die strukturellen Voraussetzungen dafür wurden festgelegt. Weitere Projektideen werden auf der Herbsttagung 2025 erneut im Plenum besprochen werden.

Capdevila, J., et al., 1706O Efficacy, safety and subgroup analysis of 177Lu-edotreotide vs everolimus in patients with grade 1 or grade 2 GEP-NETs: Phase III COMPETE trial. Annals of Oncology, 2025. 36: p. S1006.

Singh S, Halperin D, Myrehaug S, Herrmann K, Pavel M, Kunz PL, Chasen B, Tafuto S, Lastoria S, Capdevila J, García-Burillo A, Oh DY, Yoo C, Halfdanarson TR, Falk S, Folitar I, Zhang Y, Aimone P, de Herder WW, Ferone D; all the NETTER-2 Trial Investigators. 177Lu-DOTA-TATE plus long-acting octreotide versus high-dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2-3, well-differentiated, gastroentero-pancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study. Lancet. 2024 Jun 29;403(10446):2807-2817. doi: 10.1016/S0140-6736(24)00701-3. Epub 2024 Jun 5. PMID: 38851203

S. Krug, L. Apostolidis, A.O. Koenig,  A. Rinke, J. Schrader, T.J. Ettrich, H. Jann, M. Oberbeck, D. Hörsch, T.M. Gress, T. Kegel, M. Richter, S. Behl, J. Steighardt, P. Michl. Ramucirumab in combination with dacarbazine in patients with progressive well-differentiated metastatic pancreatic neuroendocrine tumors (RamuNET): An AIO phase II multicenter single-arm study. Ann Oncol S752, Volume 35- Issue S2- 2024; https://doi.org/10.1016/j.annonc.2024.08.1206

A.O. Koenig, J. Reinecke, J. Halfen, K. Lang, U. König, R.Tostmann, N. Kirchhof, T. Asendorf, D. Hörsch, A. Kröcher, M. Quante, V. Ellenrieder, N. Schulte, T. Wirth, A. Weich, L. Apostolidis, S. Krug, A. Rinke, M.E. Pavel.  Interim analysis of CABONEN: A multicenter phase II trial investigating cabozantinib in patients with advanced, low proliferative NEN G3 Ann Oncol S752, Volume 35- Issue S2- 2024; https://doi.org/10.1016/j.annonc.2024.08.1205

M.E. Pavel, D. Ferone, D. Halperin, S. Myrehaug, K. Herrmann, P.L. Kunz, B. Chasen, J. Capdevila Castillon, S. Tafuto, D. Oh, C. Yoo, S. Falk, T.R. Halfdanarson, I. Folitar, Y. Zhang, W.W. de Herder, S. Singh. A multivariate efficacy analysis of [177Lu]Lu-DOTA-TATE in the NETTER 2 study. Annals of Oncology (2024) 35 (suppl_2): S749-S761. 10.1016/annonc/annonc1598.

M.M. Weber, L. Apostolidis, S. Krug, A. Rinke, B. Gruen, P. Michl and others. 1185MO Activity and safety of avelumab alone or in combination with cabozantinib in patients with advanced high grade neuroendocrine neoplasias (NEN G3) progressing after chemotherapy. The phase II, open-label, multicenter AVENEC and CABOAVENEC trials. Ann Oncol. Volume 34, Supplement, S702, October 2023

M.E. Pavel. L. Fischer von Weikersthal, G. Klöppel K. Krause, L. Apostolidis. 1184MO Safety and efficacy of everolimus (EVE) as second-line treatment in neuroendocrine neoplasms G3 (NEN G3): An AIO phase II study (EVINEC). Annals of Oncology Vol. 34 Supplement S702, October, 2023.

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; NETTER-1 investigators. 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. Lancet Oncol. 2021 Dec;22(12):1752-1763. doi: 10.1016/S1470-2045(21)00572-6. Epub 2021 Nov 15.

Krug S, Kegel T, Gress TM, Rinke A, Apostolidis L, Jann H, König A, Hörsch D, Schrader J, Ettrich TJ, Richter M, Steighardt J, Michl P. Ramucirumab in combination with dacarbazine in patients with progressive well-differentiated metastatic pancreatic neuroendocrine tumors (RamuNET): study protocol for a multicenter single-arm trial. BMC Cancer. 2021 Nov 12;21(1):1206. doi: 10.1186/s12885-021-08900-7.

Merola E, Pascher A, Rinke A, Bartsch DK, Zerbi A, Nappo G, Carnaghi C, Ciola M, McNamara MG, Zandee W, Bertani E, Marcucci S, Modica R, Grützmann R, Fazio N, de Herder W, Valle JW, Gress TM, Fave GD, de Pretis G, Perren A, Wiedenmann B, Pavel ME. Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence. Ann Surg Oncol. 2022 Sep;29(9):5568-5577. doi: 10.1245/s10434-022-11837-1. Epub 2022 May 18.

Srirajaskanthan R, Pavel M, Kulke M, Clement D, Houchard A, Keeber L, Weickert MO. Weight Maintenance up to 48 Weeks in Patients With Carcinoid Syndrome Treated With Telotristat Ethyl: Pooled Data From the Open-Label Extensions of the Phase III Clinical Trials TELESTAR and TELECAST. Clin Ther. 2021 Sep 28:S0149-2918(21)00313-1. doi: 10.1016/j.clinthera.2021.08.014.

Pavel M, Ćwikła JB, Lombard-Bohas C, Borbath I, Shah T, Pape UF, Capdevila J, Panzuto F, Truong Thanh XM, Houchard A, Ruszniewski P. Efficacy and safety of high-dose lanreotide autogel in patients with progressive pancreatic or midgut neuroendocrine tumours: CLARINET FORTE phase 2 study results. Eur J Cancer. 2021 Sep 27;157:403-414. doi: 10.1016/j.ejca.2021.06.056.

Rinke A, Auernhammer CJ, Bodei L, Kidd M, Krug S, Lawlor R, Marinoni I, Perren A, Scarpa A, Sorbye H, Pavel ME, Weber MM, Modlin I, Gress TM. Treatment of advanced gastroenteropancreatic neuroendocrine neoplasia, are we on the way to personalised medicine? Gut. 2021 Sep;70(9):1768-1781. doi: 10.1136/gutjnl-2020-321300.

Rinke A, Maintz C, Müller L, Weber MM, Lahner H, Pavel M, Saeger W, Houchard A, Ungewiss H, Petersenn S. Multicenter, Observational Study of Lanreotide Autogel for the Treatment of Patients with Neuroendocrine Tumors in Routine Clinical Practice in Germany and Austria. Exp Clin Endocrinol Diabetes. 2021 Jul;129(7):500-509. doi: 10.1055/a-1342-2755

Hörsch D, Anthony L, Gross DJ, Valle J, Welin S, Benavent M, Caplin M, Pavel M, Bergsland E, Öberg K, Kassler-Taub KB, Binder P, Banks P, Lapuerta P, Kulke MH. Long-term Treatment with Telotristat Ethyl in Patients with Carcinoid Syndrome Symptoms: Results from the TELEPATH Study. Neuroendocrinology. 2021 May 3. doi: 10.1159/000516958

Fazio N, Carnaghi C, Buzzoni R, Valle JW, Herbst F, Ridolfi A, Strosberg J, Kulke MH, Pavel ME, Yao JC. Relationship between metabolic toxicity and efficacy of everolimus in patients with neuroendocrine tumors: A pooled analysis from the randomized, phase 3 RADIANT-3 and RADIANT-4 trials. Cancer. 2021 Aug 1;127(15):2674-2682

Chan DL, Yao JC, Carnaghi C, Buzzoni R, Herbst F, Ridolfi A, Strosberg J, Kulke MH, Pavel M, Singh S. Markers of Systemic Inflammation in Neuroendocrine Tumors: A Pooled Analysis of the RADIANT-3 and RADIANT-4 Studies. Pancreas. 2021 Feb 1;50(2):130-137. doi: 10.1097/MPA.0000000000001745

Yao JC, Strosberg J, Fazio N, Pavel ME, Bergsland E, Ruszniewski P, Halperin DM, Li D, Tafuto S, Raj N, Campana D, Hijioka S, Raderer M, Guimbaud R, Gajate P, Pusceddu S, Reising A, Degtyarev E, Shilkrut M, Eddy S, Singh S. Spartalizumab in metastatic, well/poorly-differentiated neuroendocrine neoplasms. Endocr Relat Cancer. 2021 Jan 1:ERC-20-0382.R1.

Caplin ME, Pavel M, Phan AT, Ćwikła JB, Sedláčková E, Thanh XT, Wolin EM, Ruszniewski P; CLARINET Investigators. Lanreotide autogel/depot in advanced enteropancreatic neuroendocrine tumours: final results of the CLARINET open-label extension study. Endocrine. 2021 Feb;71(2):502-513. doi: 10.1007/s12020-020-02475-2.

Dillon JS, Kulke MH, Hörsch D, Anthony LB, Warner RRP, Bergsland E, Welin S, O'Dorisio TM, 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. J Gastrointest Cancer. 2021 Mar;52(1):212-221

Krug S, Garbe J, König S, Ungewiss H, Michl P, Rinke A, Schrader J. Professional Assessment of the Impact of COVID-19 on Handling NET Patients. J Clin Med. 2020 Nov 11;9(11):3633. doi: 10.3390/jcm9113633. PMID: 33187393

Anthony LB, Kulke MH, Caplin ME, Bergsland E, Öberg K, Pavel M, Hörsch D, Warner RRP, O'Dorisio TM, Dillon JS, Lapuerta P, Kassler-Taub K, Jiang W. Long-Term Safety Experience with Telotristat Ethyl Across Five Clinical Studies in Patients with Carcinoid Syndrome. Oncologist. 2019 Aug;24(8):e662-e670. doi: 10.1634/the oncologist.2018-0236. Epub 2019 Jan 16.

Caplin ME, Pavel M, Phan AT, Ćwikła JB, Sedláčková E, Thanh XT, Wolin EM, Ruszniewski P; CLARINET Investigators. Lanreotide autogel/depot in advanced enteropancreatic neuroendocrine tumours: final results of the CLARINET open-label extension study. Endocrine. 2020 Oct 14. doi: 10.1007/s12020-020-02475-2.

Dillon JS, Kulke MH, Hörsch D, Anthony LB, Warner RRP, Bergsland E, Welin S, O'Dorisio TM, 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.  J Gastrointest Cancer.  2020 Mar 7.

Christian Fottner, Leonidas Apostolidis, Martina Ferrata, Sebastian Krug, Patrick Michl, Arno Schad, Wilfried Roth, Dirk Jaeger, Peter R. Galle, and Matthias M. Weber. A phase II, open label, multicenter trial of avelumab in patients with advanced, metastatic high-grade neuroendocrine carcinomas NEC G3 (WHO 2010) progressive after first-line chemotherapy (AVENEC). Journal of Clinical Oncology 2019 37:15_suppl, 4103-4103

Pavel ME, Baudin E, Öberg KE, Hainsworth JD, Voi M, Rouyrre N, Peeters M, Gross DJ, Yao JC. Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome: final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study. Ann Oncol. 2019 Dec 1;30(12):2010. doi: 10.1093/annonc/mdz222.

Pavel M, JB Cwikła, C Lombard-Bohas, I Borbath, T Shah, U-F Pape, X-M Truong Thanh, A Houchard, P Ruszniewski. Efficacy and safety of lanreotide autogel (LAN) 120 mg every 14 days in progressive pancreatic or midgut neuroendocrine tumours (NETs): CLARINET FORTE study results. Mini Oral presentation at ESMO Virtual Congress 2020, 19–21 September.

Anja Rinke , Maureen P Neary, Jennifer Eriksson, Matthias Hunger, Thinh Doan, Dimitra Karli, Rudolf Arnold. Health-Related Quality of Life for Long-Acting Octreotide versus Placebo in Patients with Metastatic Midgut Neuroendocrine Tumors in the Phase 3 PROMID Trial. Neuroendocrinology 2019;109(2):141-151.