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

De Vos-Geelen, J.; Venerito, Marino; Von-Werder, Alezander; Jann, Henning; Rinke, Anja; Smith, D.; Hörsch, D.; Starling, Naureen; Ruszniewski, Philippe; Baudin, Eric; Metges, J.-P.; Caroli-Bosc, F.-X.; Reed, N.S.; Manzano, José Luis; Schrader, J.; Martín, M.; Navarro Perez, Valentin; Scarpa, A.; Valentí, Víctor; Lawlor, R.T.; Hernando, Jorge; Ragulan, C.; Colao, A.M.; Ps, H.; Vestermark, Lene; Sadanandam, A.; Carnaghi, Carlo; Knigge, U.P.; Capdevila, Jaume; Tafuto, Salvatore; Krogh, M.; Teulé-Vega, Àlex; Garcia Carbonero, Rocio; Klümpen, H.-J.; Cremer, B.; Sevilla, I.; Eriksson, B.; Tabaksblat, E.; Carmona Bayonas, Alberto; Salazar Soler, Ramón; Jiménez Fonseca, Paula; Benavent Viñuales, Marta

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

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, cr...

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Autores:	De Vos-Geelen, J., Venerito, Marino, Von-Werder, Alezander, Jann, Henning, Rinke, Anja, Smith, D., Hörsch, D., Starling, Naureen, Ruszniewski, Philippe, Baudin, Eric, Metges, J.-P., Caroli-Bosc, F.-X., Reed, N.S., Manzano, José Luis, Schrader, J., Martín, M., Navarro Perez, Valentin, Scarpa, A., Valentí, Víctor, Lawlor, R.T., Hernando, Jorge, Ragulan, C., Colao, A.M., Ps, H., Vestermark, Lene, Sadanandam, A., Carnaghi, Carlo, Knigge, U.P., Capdevila, Jaume, Tafuto, Salvatore, Krogh, M., Teulé-Vega, Àlex, Garcia Carbonero, Rocio, Klümpen, H.-J., Cremer, B., Sevilla, I., Eriksson, B., Tabaksblat, E., Carmona Bayonas, Alberto, Salazar Soler, Ramón, Jiménez Fonseca, Paula, Benavent Viñuales, Marta
Formato:	artículo
Estado:	Versión publicada
Fecha de publicación:	2025
País:	España
Recursos:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/227020
Acesso em linha:	https://hdl.handle.net/2445/227020
Access Level:	acceso abierto
Palavra-chave:	Estreptomicina Streptomycin

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spelling	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 trialDe Vos-Geelen, J.Venerito, MarinoVon-Werder, AlezanderJann, HenningRinke, AnjaSmith, D.Hörsch, D.Starling, NaureenRuszniewski, PhilippeBaudin, EricMetges, J.-P.Caroli-Bosc, F.-X.Reed, N.S.Manzano, José LuisSchrader, J.Martín, M.Navarro Perez, ValentinScarpa, A.Valentí, VíctorLawlor, R.T.Hernando, JorgeRagulan, C.Colao, A.M.Ps, H.Vestermark, LeneSadanandam, A.Carnaghi, CarloKnigge, U.P.Capdevila, JaumeTafuto, SalvatoreKrogh, M.Teulé-Vega, ÀlexGarcia Carbonero, RocioKlümpen, H.-J.Cremer, B.Sevilla, I.Eriksson, B.Tabaksblat, E.Carmona Bayonas, AlbertoSalazar Soler, RamónJiménez Fonseca, PaulaBenavent Viñuales, MartaEstreptomicinaStreptomycinBackground: 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-mPFS1). Results: Patients were randomized to everolimus (n = 72) or STZ/5-FU (n = 69) first. The 12-mPFS1 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 PFS1 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. Keywords: 5-fluorouracil; advanced pancreatic neuroendocrine neoplasm; everolimus; panNET; sequential strategy; streptozotocin.Elsevier2026202620252026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10 p.application/pdfhttps://hdl.handle.net/2445/227020Articles publicats en revistes (Ciències Clíniques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.esmoop.2025.105922ESMO Open, 2025, vol. 12https://doi.org/10.1016/j.esmoop.2025.105922cc-by-nc-nd (c) European Society for Medical Oncology, CH, 2025http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2270202026-05-29T05:05:01Z
dc.title.none.fl_str_mv	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
title	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
spellingShingle	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 De Vos-Geelen, J. Estreptomicina Streptomycin
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
dc.creator.none.fl_str_mv	De Vos-Geelen, J. Venerito, Marino Von-Werder, Alezander Jann, Henning Rinke, Anja Smith, D. Hörsch, D. Starling, Naureen Ruszniewski, Philippe Baudin, Eric Metges, J.-P. Caroli-Bosc, F.-X. Reed, N.S. Manzano, José Luis Schrader, J. Martín, M. Navarro Perez, Valentin Scarpa, A. Valentí, Víctor Lawlor, R.T. Hernando, Jorge Ragulan, C. Colao, A.M. Ps, H. Vestermark, Lene Sadanandam, A. Carnaghi, Carlo Knigge, U.P. Capdevila, Jaume Tafuto, Salvatore Krogh, M. Teulé-Vega, Àlex Garcia Carbonero, Rocio Klümpen, H.-J. Cremer, B. Sevilla, I. Eriksson, B. Tabaksblat, E. Carmona Bayonas, Alberto Salazar Soler, Ramón Jiménez Fonseca, Paula Benavent Viñuales, Marta
author	De Vos-Geelen, J.
author_facet	De Vos-Geelen, J. Venerito, Marino Von-Werder, Alezander Jann, Henning Rinke, Anja Smith, D. Hörsch, D. Starling, Naureen Ruszniewski, Philippe Baudin, Eric Metges, J.-P. Caroli-Bosc, F.-X. Reed, N.S. Manzano, José Luis Schrader, J. Martín, M. Navarro Perez, Valentin Scarpa, A. Valentí, Víctor Lawlor, R.T. Hernando, Jorge Ragulan, C. Colao, A.M. Ps, H. Vestermark, Lene Sadanandam, A. Carnaghi, Carlo Knigge, U.P. Capdevila, Jaume Tafuto, Salvatore Krogh, M. Teulé-Vega, Àlex Garcia Carbonero, Rocio Klümpen, H.-J. Cremer, B. Sevilla, I. Eriksson, B. Tabaksblat, E. Carmona Bayonas, Alberto Salazar Soler, Ramón Jiménez Fonseca, Paula Benavent Viñuales, Marta
author_role	author
author2	Venerito, Marino Von-Werder, Alezander Jann, Henning Rinke, Anja Smith, D. Hörsch, D. Starling, Naureen Ruszniewski, Philippe Baudin, Eric Metges, J.-P. Caroli-Bosc, F.-X. Reed, N.S. Manzano, José Luis Schrader, J. Martín, M. Navarro Perez, Valentin Scarpa, A. Valentí, Víctor Lawlor, R.T. Hernando, Jorge Ragulan, C. Colao, A.M. Ps, H. Vestermark, Lene Sadanandam, A. Carnaghi, Carlo Knigge, U.P. Capdevila, Jaume Tafuto, Salvatore Krogh, M. Teulé-Vega, Àlex Garcia Carbonero, Rocio Klümpen, H.-J. Cremer, B. Sevilla, I. Eriksson, B. Tabaksblat, E. Carmona Bayonas, Alberto Salazar Soler, Ramón Jiménez Fonseca, Paula Benavent Viñuales, Marta
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Estreptomicina Streptomycin
topic	Estreptomicina Streptomycin
description	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-mPFS1). Results: Patients were randomized to everolimus (n = 72) or STZ/5-FU (n = 69) first. The 12-mPFS1 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 PFS1 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. Keywords: 5-fluorouracil; advanced pancreatic neuroendocrine neoplasm; everolimus; panNET; sequential strategy; streptozotocin.
publishDate	2025
dc.date.none.fl_str_mv	2025 2026 2026 2026
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/227020
url	https://hdl.handle.net/2445/227020
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1016/j.esmoop.2025.105922 ESMO Open, 2025, vol. 12 https://doi.org/10.1016/j.esmoop.2025.105922
dc.rights.none.fl_str_mv	cc-by-nc-nd (c) European Society for Medical Oncology, CH, 2025 http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by-nc-nd (c) European Society for Medical Oncology, CH, 2025 http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	10 p. application/pdf
dc.publisher.none.fl_str_mv	Elsevier
publisher.none.fl_str_mv	Elsevier
dc.source.none.fl_str_mv	Articles publicats en revistes (Ciències Clíniques) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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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

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