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-pos...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 2025
|
| In: |
Gynecologic oncology
Year: 2025, Volume: 192, Pages: 128-136 |
| ISSN: | 1095-6859 |
| DOI: | 10.1016/j.ygyno.2024.12.003 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ygyno.2024.12.003 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0090825824012204 
|
| Author Notes: | Mansoor R. Mirza, Line Bjørge, Frederik Marmé, René DePont Christensen, Marta Gil-Martin, Annika Auranen, Beyhan Ataseven, Maria Jesús Rubio, Vanda Salutari, Adam A. Luczak, Ingo B. Runnebaum, Andrés Redondo, Kristina Lindemann, Fabian Trillsch, M. Pilar Barretina Ginesta, Henrik Roed, Jean-Emmanuel Kurtz, Karen S. Petersson, Gitte-Bettina Nyvang, Jalid Sehouli |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1925447553 | ||
| 003 | DE-627 | ||
| 005 | 20250913141520.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 250513s2025 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ygyno.2024.12.003 |2 doi | |
| 035 | |a (DE-627)1925447553 | ||
| 035 | |a (DE-599)KXP1925447553 | ||
| 035 | |a (OCoLC)1528045360 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Mirza, Mansoor R. |e VerfasserIn |0 (DE-588)1365428044 |0 (DE-627)1925448096 |4 aut | |
| 245 | 1 | 0 | |a Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer |b double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial |c Mansoor R. Mirza, Line Bjørge, Frederik Marmé, René DePont Christensen, Marta Gil-Martin, Annika Auranen, Beyhan Ataseven, Maria Jesús Rubio, Vanda Salutari, Adam A. Luczak, Ingo B. Runnebaum, Andrés Redondo, Kristina Lindemann, Fabian Trillsch, M. Pilar Barretina Ginesta, Henrik Roed, Jean-Emmanuel Kurtz, Karen S. Petersson, Gitte-Bettina Nyvang, Jalid Sehouli |
| 264 | 1 | |c January 2025 | |
| 300 | |b Diagramme | ||
| 300 | |a 9 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online verfügbar: 9. Dezember 2024, Artikelversion: 9. Dezember 2024 | ||
| 500 | |a Gesehen am 13.05.2025 | ||
| 520 | |a 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/recurrent endometrial cancer. - Patients and methods - This placebo-controlled double-blind, randomized phase II screening trial (NCT02730429) enrolled women with measurable/evaluable estrogen receptor-positive endometrioid endometrial 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 | ||
| 650 | 4 | |a CDK4/6 inhibitor | |
| 650 | 4 | |a Endometrial cancer | |
| 650 | 4 | |a Estrogen receptor-positive | |
| 650 | 4 | |a Hormonal therapy | |
| 650 | 4 | |a Letrozole | |
| 650 | 4 | |a Palbociclib | |
| 700 | 1 | |a Bjørge, Line |e VerfasserIn |4 aut | |
| 700 | 1 | |a Marmé, Frederik |d 1974- |e VerfasserIn |0 (DE-588)132561972 |0 (DE-627)52394893X |0 (DE-576)299226549 |4 aut | |
| 700 | 1 | |a Christensen, René DePont |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gil-Martin, Marta |e VerfasserIn |4 aut | |
| 700 | 1 | |a Auranen, Annika |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ataseven, Beyhan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rubio, Maria Jesús |e VerfasserIn |4 aut | |
| 700 | 1 | |a Salutari, Vanda |e VerfasserIn |4 aut | |
| 700 | 1 | |a Luczak, Adam A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Runnebaum, Ingo B. |d 1960- |e VerfasserIn |0 (DE-588)1111567727 |0 (DE-627)865636184 |0 (DE-576)476172144 |4 aut | |
| 700 | 1 | |a Redondo, Andrés |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lindemann, Kristina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Trillsch, Fabian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ginesta, M. Pilar Barretina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Roed, Henrik |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kurtz, Jean-Emmanuel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Petersson, Karen S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nyvang, Gitte-Bettina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sehouli, Jalid |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Gynecologic oncology |d Orlando, Fla. : Academic Press, 1972 |g 192(2025) vom: Jan., Seite 128-136 |h Online-Ressource |w (DE-627)266881351 |w (DE-600)1467974-7 |w (DE-576)104193735 |x 1095-6859 |7 nnas |a Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial |
| 773 | 1 | 8 | |g volume:192 |g year:2025 |g month:01 |g pages:128-136 |g extent:9 |a Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.ygyno.2024.12.003 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S0090825824012204 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20250513 | ||
| 993 | |a Article | ||
| 994 | |a 2025 | ||
| 998 | |g 132561972 |a Marmé, Frederik |m 132561972:Marmé, Frederik |d 60000 |d 61300 |d 50000 |e 60000PM132561972 |e 61300PM132561972 |e 50000PM132561972 |k 0/60000/ |k 1/60000/61300/ |k 0/50000/ |p 3 | ||
| 999 | |a KXP-PPN1925447553 |e 4723807187 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"display":"Mirza, Mansoor R.","given":"Mansoor R.","role":"aut","family":"Mirza"},{"role":"aut","given":"Line","display":"Bjørge, Line","family":"Bjørge"},{"family":"Marmé","given":"Frederik","role":"aut","display":"Marmé, Frederik"},{"family":"Christensen","display":"Christensen, René DePont","role":"aut","given":"René DePont"},{"given":"Marta","role":"aut","display":"Gil-Martin, Marta","family":"Gil-Martin"},{"display":"Auranen, Annika","role":"aut","given":"Annika","family":"Auranen"},{"display":"Ataseven, Beyhan","given":"Beyhan","role":"aut","family":"Ataseven"},{"family":"Rubio","role":"aut","given":"Maria Jesús","display":"Rubio, Maria Jesús"},{"display":"Salutari, Vanda","role":"aut","given":"Vanda","family":"Salutari"},{"display":"Luczak, Adam A.","role":"aut","given":"Adam A.","family":"Luczak"},{"given":"Ingo B.","role":"aut","display":"Runnebaum, Ingo B.","family":"Runnebaum"},{"family":"Redondo","display":"Redondo, Andrés","role":"aut","given":"Andrés"},{"family":"Lindemann","given":"Kristina","role":"aut","display":"Lindemann, Kristina"},{"family":"Trillsch","display":"Trillsch, Fabian","role":"aut","given":"Fabian"},{"role":"aut","given":"M. Pilar Barretina","display":"Ginesta, M. Pilar Barretina","family":"Ginesta"},{"role":"aut","given":"Henrik","display":"Roed, Henrik","family":"Roed"},{"family":"Kurtz","display":"Kurtz, Jean-Emmanuel","role":"aut","given":"Jean-Emmanuel"},{"family":"Petersson","display":"Petersson, Karen S.","role":"aut","given":"Karen S."},{"role":"aut","given":"Gitte-Bettina","display":"Nyvang, Gitte-Bettina","family":"Nyvang"},{"family":"Sehouli","given":"Jalid","role":"aut","display":"Sehouli, Jalid"}],"recId":"1925447553","note":["Online verfügbar: 9. Dezember 2024, Artikelversion: 9. Dezember 2024","Gesehen am 13.05.2025"],"title":[{"title_sort":"Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer","title":"Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer","subtitle":"double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial"}],"id":{"doi":["10.1016/j.ygyno.2024.12.003"],"eki":["1925447553"]},"type":{"media":"Online-Ressource","bibl":"article-journal"},"name":{"displayForm":["Mansoor R. Mirza, Line Bjørge, Frederik Marmé, René DePont Christensen, Marta Gil-Martin, Annika Auranen, Beyhan Ataseven, Maria Jesús Rubio, Vanda Salutari, Adam A. Luczak, Ingo B. Runnebaum, Andrés Redondo, Kristina Lindemann, Fabian Trillsch, M. Pilar Barretina Ginesta, Henrik Roed, Jean-Emmanuel Kurtz, Karen S. Petersson, Gitte-Bettina Nyvang, Jalid Sehouli"]},"relHost":[{"note":["Gesehen am 12.02.20"],"recId":"266881351","title":[{"subtitle":"an international journal ; official publication of the Society of Gynecologic Oncologists [u.a.]","title":"Gynecologic oncology","title_sort":"Gynecologic oncology"}],"id":{"zdb":["1467974-7"],"eki":["266881351"],"issn":["1095-6859"]},"type":{"media":"Online-Ressource","bibl":"periodical"},"corporate":[{"display":"Society of Gynecologic Oncology","role":"isb"}],"pubHistory":["1.1972/73 -"],"disp":"Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trialGynecologic oncology","part":{"pages":"128-136","extent":"9","year":"2025","text":"192(2025) vom: Jan., Seite 128-136","volume":"192"},"language":["eng"],"physDesc":[{"extent":"Online-Ressource"}],"origin":[{"publisher":"Academic Press ; Elsevier","publisherPlace":"Orlando, Fla. ; Amsterdam [u.a.]","dateIssuedDisp":"1972-","dateIssuedKey":"1972"}]}],"language":["eng"],"origin":[{"dateIssuedKey":"2025","dateIssuedDisp":"January 2025"}],"physDesc":[{"extent":"9 S.","noteIll":"Diagramme"}]} | ||
| SRT | |a MIRZAMANSOPALBOCICLI2025 | ||