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 |
| Summary: | 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 |
|---|---|
| Item Description: | Online verfügbar: 9. Dezember 2024, Artikelversion: 9. Dezember 2024 Gesehen am 13.05.2025 |
| Physical Description: | Online Resource |
| ISSN: | 1095-6859 |
| DOI: | 10.1016/j.ygyno.2024.12.003 |