Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial

Purpose. The CDK4/6 inhibitor palbociclib inhibits cyclin A, which is overexpressed in endometrial cancer. Combining palbociclib with endocrine therapy improves efficacy in hormone receptor-positive breast cancer. We investigated palbociclib combined with endocrine therapy for estrogen receptor-posi...

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Autores: Mirza, Mansoor R., Bjørge, Line, Marmé, Frederik, Christensen, René Depont, Gil Martin, Marta, Auranen, Annika, Ataseven, Beyhan, Rubio, Maria Jesús, Salutari, Vanda, Luczak, Adam A., Runnebaum, Ingo B., Redondo, Andrés, Lindemann, Kristina, Trillsch, Fabian, Barretina Ginesta, M. Pilar, Roed, Henrik, Kurtz, Jean Emmanuel, Petersson, Karen S., Nyvang, Gitte Bettina, Sehouli, Jalid
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución: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:2445/219582
Acceso en línea:https://hdl.handle.net/2445/219582
Access Level:acceso abierto
Palabra clave:Càncer d'endometri
Hormonoteràpia
Endometrial cancer
Hormone therapy
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spelling Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trialMirza, Mansoor R.Bjørge, LineMarmé, FrederikChristensen, René DepontGil Martin, MartaAuranen, AnnikaAtaseven, BeyhanRubio, Maria JesúsSalutari, VandaLuczak, Adam A.Runnebaum, Ingo B.Redondo, AndrésLindemann, KristinaTrillsch, FabianBarretina Ginesta, M. PilarRoed, HenrikKurtz, Jean EmmanuelPetersson, Karen S.Nyvang, Gitte BettinaSehouli, JalidCàncer d'endometriHormonoteràpiaEndometrial cancerHormone therapyPurpose. The CDK4/6 inhibitor palbociclib inhibits cyclin A, which is overexpressed in endometrial cancer. Combining palbociclib with endocrine therapy improves efficacy in hormone receptor-positive breast cancer. We investigated palbociclib combined with endocrine therapy for estrogen receptor-positive advanced/recur-rent endometrial cancer. Patients and methods. Thi s placebo-controlled double-blind, randomized phase II screening trial (NCT02730429) enrolled women with measurable/evaluable estrogen receptor-positive endometrioid endome-trial cancer that was primary metastatic or had relapsed after >= 1 prior systemic therapy. Patients were randomized in a 1:1 ratio, stratified by number of prior chemotherapy lines, measurable versus evaluable non- measurable disease, and prior medroxyprogesterone/megestrol acetate treatment, to receive oral letrozole 2.5 mg on days 1-28 plus either oral palbociclib 125 mg or placebo on days 1-21, repeated every 28 days until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression- free survival (PFS). Results. Among 77 patients randomized between February 16, 2017, and December 21, 2018, 73 were treated (36 with palbociclib-letrozole, 37 with placebo-letrozole). Median follow-up was 21.9 (95 % CI, 16.7 to 22.3) months. Median PFS was 8.3 (95 % CI, 4.6 to 11.2) versus 3.1 (95 % CI, 2.7 to 6.8) months, respectively. In a landmark analysis at 12 months the PFS hazard ratio was 0.57 (95 % CI, 0.32 to 0.99; P = .044). Grade >= 3 adverse events were more common with palbociclib-letrozole (67 %) than placebo-letrozole (30 %), most commonly neutropenia (44 % v 0 %, respectively) . Conclusion. These results support a potential role of the palbociclib-letrozole combination as treatment for hormone receptor-positive advanced/recurrent endometrial cancer. Based on these encouraging results, phase III evaluation of letrozole combined with a CDK4/6 inhibitor is planned. Clinical trial information. NCT02730429 (c) 2024 Published by Elsevier Inc.Elsevier BV2025202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfhttps://hdl.handle.net/2445/219582Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))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.ygyno.2024.12.003Gynecologic Oncology, 2025, vol. 192, p. 128-136https://doi.org/10.1016/j.ygyno.2024.12.003cc-by (c) Mirza, Mansoor R. et al., 2024http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2195822026-05-29T05:05:01Z
dc.title.none.fl_str_mv Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial
title Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial
spellingShingle Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial
Mirza, Mansoor R.
Càncer d'endometri
Hormonoteràpia
Endometrial cancer
Hormone therapy
title_short Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial
title_full Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial
title_fullStr Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial
title_full_unstemmed Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial
title_sort Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial
dc.creator.none.fl_str_mv Mirza, Mansoor R.
Bjørge, Line
Marmé, Frederik
Christensen, René Depont
Gil Martin, Marta
Auranen, Annika
Ataseven, Beyhan
Rubio, Maria Jesús
Salutari, Vanda
Luczak, Adam A.
Runnebaum, Ingo B.
Redondo, Andrés
Lindemann, Kristina
Trillsch, Fabian
Barretina Ginesta, M. Pilar
Roed, Henrik
Kurtz, Jean Emmanuel
Petersson, Karen S.
Nyvang, Gitte Bettina
Sehouli, Jalid
author Mirza, Mansoor R.
author_facet Mirza, Mansoor R.
Bjørge, Line
Marmé, Frederik
Christensen, René Depont
Gil Martin, Marta
Auranen, Annika
Ataseven, Beyhan
Rubio, Maria Jesús
Salutari, Vanda
Luczak, Adam A.
Runnebaum, Ingo B.
Redondo, Andrés
Lindemann, Kristina
Trillsch, Fabian
Barretina Ginesta, M. Pilar
Roed, Henrik
Kurtz, Jean Emmanuel
Petersson, Karen S.
Nyvang, Gitte Bettina
Sehouli, Jalid
author_role author
author2 Bjørge, Line
Marmé, Frederik
Christensen, René Depont
Gil Martin, Marta
Auranen, Annika
Ataseven, Beyhan
Rubio, Maria Jesús
Salutari, Vanda
Luczak, Adam A.
Runnebaum, Ingo B.
Redondo, Andrés
Lindemann, Kristina
Trillsch, Fabian
Barretina Ginesta, M. Pilar
Roed, Henrik
Kurtz, Jean Emmanuel
Petersson, Karen S.
Nyvang, Gitte Bettina
Sehouli, Jalid
author2_role 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 Càncer d'endometri
Hormonoteràpia
Endometrial cancer
Hormone therapy
topic Càncer d'endometri
Hormonoteràpia
Endometrial cancer
Hormone therapy
description Purpose. The CDK4/6 inhibitor palbociclib inhibits cyclin A, which is overexpressed in endometrial cancer. Combining palbociclib with endocrine therapy improves efficacy in hormone receptor-positive breast cancer. We investigated palbociclib combined with endocrine therapy for estrogen receptor-positive advanced/recur-rent endometrial cancer. Patients and methods. Thi s placebo-controlled double-blind, randomized phase II screening trial (NCT02730429) enrolled women with measurable/evaluable estrogen receptor-positive endometrioid endome-trial cancer that was primary metastatic or had relapsed after >= 1 prior systemic therapy. Patients were randomized in a 1:1 ratio, stratified by number of prior chemotherapy lines, measurable versus evaluable non- measurable disease, and prior medroxyprogesterone/megestrol acetate treatment, to receive oral letrozole 2.5 mg on days 1-28 plus either oral palbociclib 125 mg or placebo on days 1-21, repeated every 28 days until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression- free survival (PFS). Results. Among 77 patients randomized between February 16, 2017, and December 21, 2018, 73 were treated (36 with palbociclib-letrozole, 37 with placebo-letrozole). Median follow-up was 21.9 (95 % CI, 16.7 to 22.3) months. Median PFS was 8.3 (95 % CI, 4.6 to 11.2) versus 3.1 (95 % CI, 2.7 to 6.8) months, respectively. In a landmark analysis at 12 months the PFS hazard ratio was 0.57 (95 % CI, 0.32 to 0.99; P = .044). Grade >= 3 adverse events were more common with palbociclib-letrozole (67 %) than placebo-letrozole (30 %), most commonly neutropenia (44 % v 0 %, respectively) . Conclusion. These results support a potential role of the palbociclib-letrozole combination as treatment for hormone receptor-positive advanced/recurrent endometrial cancer. Based on these encouraging results, phase III evaluation of letrozole combined with a CDK4/6 inhibitor is planned. Clinical trial information. NCT02730429 (c) 2024 Published by Elsevier Inc.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
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/2445/219582
url https://hdl.handle.net/2445/219582
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.ygyno.2024.12.003
Gynecologic Oncology, 2025, vol. 192, p. 128-136
https://doi.org/10.1016/j.ygyno.2024.12.003
dc.rights.none.fl_str_mv cc-by (c) Mirza, Mansoor R. et al., 2024
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Mirza, Mansoor R. et al., 2024
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
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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score 15,81155

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