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Publications

Journal Article Ahead of print

PubMed: 41337860 DOI: 10.1016/j.esmoop.2025.105922

Streptozotocin plus 5-fluorouracil followed by everolimus or the reverse sequence in patients with advanced pancreatic neuroendocrine tumors (SEQTOR-GETNE phase III study): a randomized clinical trial.

ESMO Open 10(12):105922

Authors: J Capdevila, S Tafuto, M Krogh, A Teulé, R Garcia-Carbonero, H-J Klümpen, B Cremer, I Sevilla, B Eriksson, E Tabaksblat, J-P Metges, N S Reed, J Schrader, V Navarro, V Valentí, J Hernando, A M Colao, L Vestermark, C Carnaghi, U P Knigge, P Jimenez-Fonseca, M Benavent, J de Vos-Geelen, M Venerito, A Von Werder, H Jann, A Rinke, D Smith, D Hörsch, N Starling, P Ruszniewski, E Baudin, F-X Caroli-Bosc, J L Manzano, M Martín, A Scarpa, R T Lawlor, C Ragulan, H Ps, A Sadanandam, A Carmona-Bayonas, R Salazar

Affiliations

  • Department of Medical Oncology, Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Neuroendocrine and Endocrine Tumor Translational Research Program (NET-VHIO), Vall Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
  • Sarcomas and Rare Tumors Unit, Istituto Nazionale Tumori IRCCS, Fondazione 'G.Pascale', Naples, Italy.
  • Medical Oncology Department, Odense University Hospital, Odense, Denmark.
  • Medical Oncology Department, Oncobell Program, IDIBELL, Institut Català d'Oncologia (ICO) Hospital Duran i Reynals, Barcelona, Spain; Clinical Sciences Department, Bellvitge Campus, University of Barcelona, CIBERONC, Barcelona, Spain.
  • Medical Oncology Department, Hospital Universitario 12 de Octubre, Imas12, UCM, Madrid, Spain.
  • Medical Oncology Department, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  • Medical Oncology Department, Universitätsklinikum Köln (AöR), Köln, Germany.
  • Medical Oncology Department, Investigación Clínica y Traslacional en Cáncer, Instituto de Investigaciones Biomédicas de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria de Málaga, Málaga, Spain.
  • Endocrine Oncology Department, Uppsala University Hospital, Uppsala, Sweden.
  • Medical Oncology Department, Aarhus University Hospital, ENETS Center of Excellence, Aarhus, Denmark.
  • Medical Oncology Department, Brest Hôpital Augustin Morvan, Institut de Cancero-Hemato, Brest, France.
  • Medical Oncology Department, Beatson Oncology Centre, Glasgow, UK.
  • Medical Oncology Department, Hamburg Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
  • Clinical Research Unit, Institut Català d'Oncologia (ICO), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Medical Oncology Department, Humanitas Cancer Center, Milano, Italy.
  • Department of Endocrinology, ENETS Center of Excellence, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • Medical Oncology Department, Hospital Universitario Central de Asturias, ISPA, Oviedo, Spain.
  • Medical Oncology Department, University Hospital Virgen del Rocío, Seville Institute of Biomedicine (IBIS), Seville, Spain.
  • Medical Oncology Department, GROW - Research Institute for Oncology & Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands.
  • Department of Gastroenterology, Hepatology and Infectious Diseases, Universitätsklinikum Magdeburg A. ö. R, Magdeburg, Germany.
  • Medical Oncology Department, München rechts der Isar II, Medizinische Klinik und Poliklinik, München, Germany.
  • Medical Oncology Department, Berlin Charité Universitätsmedizin, Berlin, Germany.
  • Department of Gastroenterology, Marburg Universitätsklinikum Giessen und Marburg, Marburg, Germany; Philipps University Marburg, Marburg, Germany.
  • Medical Oncology Department, Bordeaux University Hospital-CHU Bordeaux, Hôpital Saint-André, Bordeaux, France.
  • Medical Oncology Department, Bad Berka ChA Klinik für Innere Medizin, Bad Berka, Germany.
  • Medical Oncology Department, The Royal Marsden NHS Foundation Trust, Sutton, UK.
  • Medical Oncology Department, Université Paris Cité, Beaujon Hospital, APHP, Clichy, France.
  • Medical Oncology Department, Villejuif Institut Gustave-Roussy, Paris, France.
  • Medical Oncology Department, Unité Transversale de Thérapeutiques Innovantes en Oncologie Médicale (UTTIOM), Centre Hospitalier Universitaire (CHU) Angers, Angers, France.
  • Medical Oncology Department, Institut Català d'Oncologia (ICO), ICO-Badalona, H. Germans Trias i Pujol, Badalona, Barcelona, Spain.
  • Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
  • ARC-Net Research Center, University and Hospital Trust of Verona, Verona, Italy; Department of Diagnostics and Public Health, Section of Pathology, and Department of Engineering for Innovative Medicine, University of Verona, Verona, Italy.
  • Division of Molecular Pathology, Institute of Cancer Research, London, UK.
  • Medical Oncology Department, Hospital General Universitario Morales Meseguer, UMU, IMIB, Murcia, Spain.
  • Medical Oncology Department, Oncobell Program, IDIBELL, Institut Català d'Oncologia (ICO) Hospital Duran i Reynals, Barcelona, Spain; Clinical Sciences Department, Bellvitge Campus, University of Barcelona, CIBERONC, Barcelona, Spain.

Abstract

BACKGROUND

Everolimus or streptozotocin plus 5-fluorouracil (STZ/5-FU) are approved treatments for patients with pancreatic neuroendocrine tumors (panNETs). The SEQTOR trial aimed to assess the optimal treatment sequence.

PATIENTS AND METHODS

SEQTOR was an international, open-label, randomized, crossover, phase III trial that recruited adults with unresectable or metastatic, advanced, well-differentiated panNET. Patients received 10 mg/day of everolimus followed upon progression by STZ/5-FU; or the reverse sequence. The primary endpoint was the 35-month progression-free survival (PFS) rate after first- and second-line treatment; however, due to slow accrual and longer survival, it was changed to the 12-month PFS rate following first-line treatment (12-mPFS 1).

RESULTS

Patients were randomized to everolimus (n = 72) or STZ/5-FU (n = 69) first. The 12-mPFS 1 was 71.4% [95% confidence interval (CI) 59.4% to 81.6%] and 61.8% (95% CI 49.2% to 73.3%) (odds ratio 0.65, 95% CI 0.32-1.32) with a median PFS 1 of 19.4 versus 22.7 months for everolimus and STZ/5-FU, respectively. STZ/5-FU achieved a significantly higher overall response rate in first-line (11.6% versus 30.3%, P = 0.012) and second-line (30.6% versus 9.1%, P = 0.072) treatments. No differences were shown in overall survival (median 61.7 versus 50.6 months in everolimus first and STZ/5-FU first, respectively; hazard ratio 1.43, 95% CI 0.86-2.37). Discontinuations of everolimus were more frequent.

CONCLUSION

STZ/5-FU and everolimus were not statistically different in PFS rates, but STZ/5-FU achieved higher response rates.

MeSH

Neoplasms, Fluorouracil, Everolimus, Streptozocin, Neuroendocrine Tumors, Therapeutics