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

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology Pub Date : 2025-01-01 DOI:10.1016/j.ygyno.2024.12.003

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

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引用次数: 0

Abstract

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

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帕博西尼联合来曲唑治疗雌激素受体阳性晚期/复发性子宫内膜癌：双盲安慰剂对照随机II期ENGOT-EN3/PALEO试验

目的：CDK4/6抑制剂palbociclib抑制细胞周期蛋白A在子宫内膜癌中的过表达。帕博西尼联合内分泌治疗可提高激素受体阳性乳腺癌的疗效。我们研究了帕博西尼联合内分泌治疗雌激素受体阳性晚期/复发子宫内膜癌。患者和方法：这项安慰剂对照双盲、随机II期筛查试验（NCT02730429）招募了可测量/可评估的雌激素受体阳性子宫内膜样子宫内膜癌，原发转移或在既往系统性治疗≥1次后复发的女性。患者按1:1的比例随机分组，根据既往化疗线的数量、可测量的疾病与可评估的不可测量的疾病以及既往甲孕酮/醋酸甲地孕酮治疗进行分层，在第1-28天接受口服来曲唑2.5 mg，在第1-21天接受口服帕博西尼125 mg或安慰剂，每28天重复一次，直到疾病进展或不可接受的毒性。主要终点是研究者评估的无进展生存期（PFS）。结果：在2017年2月16日至2018年12月21日期间随机选取的77例患者中，有73例接受了治疗（36例使用帕博西利-来曲唑，37例使用安慰剂-来曲唑）。中位随访时间为21.9个月（95% CI, 16.7 - 22.3）。中位PFS分别为8.3个月（95% CI, 4.6 - 11.2）和3.1个月（95% CI, 2.7 - 6.8）。在12个月的里程碑式分析中，PFS风险比为0.57 (95% CI， 0.32至0.99；p = .044)。帕博西利-来曲唑组≥3级不良事件（67%）比安慰剂-来曲唑组（30%）更常见，最常见的是中性粒细胞减少症（分别为44%和0%）。结论：这些结果支持帕博西利-来曲唑联合治疗激素受体阳性晚期/复发子宫内膜癌的潜在作用。基于这些令人鼓舞的结果，来曲唑联合CDK4/6抑制剂的III期评估正在计划中。临床试验信息：NCT02730429。

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来源期刊

Gynecologic oncology 医学-妇产科学

CiteScore

8.60

自引率

6.40%

发文量

1062

审稿时长

37 days

期刊介绍： Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy