Phase III Study Evaluating Palbociclib (PD-0332991), a Cyclin-Dependent Kinase (CDK) 4/6 Inhibitor in Patients With Hormone-receptor-positive, HER2-normal Primary Breast Cancer With High Relapse Risk After Neoadjuvant Chemotherapy "PENELOPEB"
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,250
- 试验地点
- 11
- 主要终点
- Invasive Disease Free Survival (iDFS) for Palbociclib vs. Placebo in Patients With High CPS-EG Score After Neoadjuvant Chemotherapy Receiving Standard Adjuvant Endocrine Therapy for HR-positive/HER2-normal Primary Breast Cancer.
研究概览
简要总结
The PENELOPEB study is designed to demonstrate that, in the background of standard anti-hormonal therapy, palbociclib provides superior invasive disease-free survival (iDFS) compared to placebo in pre- and postmenopausal women with HR-positive/HER2-normal early breast cancer at high risk of relapse after showing less than pathological complete response to neoadjuvant taxane- containing chemotherapy. Considering the high risk of recurrence in patients after neoadjuvant chemotherapy and a high CPS-EG score, palbociclib appears to be an attractive option with a favourable safety profile for these patients.
详细描述
Introduction:
Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer who receive chemotherapy as part of their primary treatment are at higher risk of relapse. About a third of the patients with residual invasive disease after neoadjuvant chemotherapy (NACT) will relapse despite adjuvant endocrine therapy (ET). The risk of relapse can be assessed more accurately using the clinical pathological staging-estrogen receptor grading (CPS-EG) scoring system. This involves the tumor stage before treatment start and at surgery, the estrogen receptor (ER) status, and the pathologic grading. A higher score indicates a higher risk of relapse. Patients with a score of three and higher had a disease-free survival of 70% at 5 years despite receiving ET. When combined with the group having a CPS-EG score of two and involved lymph nodes, the disease-free survival increased to 77%. This group comprises about 25% of all patients with residual disease after NACT.
Therapeutic inhibition of cyclin-dependent kinase 4 and 6 (CDK4/6) by palbociclib combined with ET demonstrated clinically relevant efficacy in metastatic HR+ and HER2- breast cancer irrespective of biomarker selection. After the pivotal PALOMA-1 trial, which led to accelerated approval of palbociclib in February 2015, further phase III trials demonstrated that the use of CDK4/6 inhibitors in pre- and postmenopausal patients with hormone-sensitive or resistant cancers, in first-line and pretreated metastatic breast cancer, improves progression-free and overall survival (OS).
Thus, we hypothesized that palbociclib may also be active in patients with residual disease after NACT who are at high risk of relapse. Based on the data from PALOMA-1, we designed the PENELOPE-B trial assessing the efficacy of one year palbociclib vs placebo added to any ET in HR+ and HER2- breast cancer patients with residual disease and high risk after NACT, based on the CPS-EG score.
Patient Selection and Study Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Palbociclib
Palbociclib at a dose of 125 mg once daily, day 1 to day 21 followed by 7 days off treatment in a 28-day cycle for thirteen cycles
干预措施: Palbociclib PD-0332991 (Drug)
Placebo
Placebo of palbociclib once daily day 1 to day 21 followed by 7 days off treatment in a28-day cycle for thirteen cycles
干预措施: Placebo (Drug)
结局指标
主要结局
Invasive Disease Free Survival (iDFS) for Palbociclib vs. Placebo in Patients With High CPS-EG Score After Neoadjuvant Chemotherapy Receiving Standard Adjuvant Endocrine Therapy for HR-positive/HER2-normal Primary Breast Cancer.
时间窗: From date of randomisation to data cut off: 24 August 2020 (approximately 6 years and 6 months)
Invasive disease-free survival (iDFS) is defined according to Hudis (J Clin Oncol 2007) as the time period between randomization and first event (ipsi- or contralateral invasive in-breast or loco-regional recurrence, distant recurrence, death from breast cancer, death from non-breast cancer cause, death from unknown cause, invasive contralateral breast cancer, second primary invasive cancer (non-breast)) assessed until the end of study.
次要结局
- iDFS Excluding Second Non-breast Cancers(From date of randomisation to data cut off: 24 August 2020 (approximately 6 years and 6 months))
- Distant Disease Free Survival (DDFS)(From date of randomisation to data cut off: 24 August 2020 (approximately 6 years and 6 months))
- Overall Survival (OS)(From date of randomisation to data cut off: 24 August 2020 (approximately 6 years and 6 months))