Intro text: 

A study of palbociclib in addition to standard endocrine treatment in hormone receptor positive Her2 normal breast cancer patients with residual disease after neoadjuvant chemotherapy and surgery

The PENELOPE-B study is designed to demonstrate that, when used with standard endocrine therapy, palbociclib provides superior invasive disease-free survival (iDFS) compared to placebo in pre- and postmenopausal women with hormone receptor (HR)-positive/HER2-normal early breast cancer at high risk of relapse after showing less than pathological complete response to neoadjuvant taxane- containing chemotherapy.
Treatment with palbociclib may be an attractive option with a favourable safety profile for these patients.

About one third of patients with HR-positive, HER2-normal breast cancer and residual disease after neoadjuvant chemotherapy have a substantial risk of relapse. The clinical-pathologic stage--estrogen/grade (CPS-EG)1 – which combines clinical stage before neoadjuvant treatment, pathological stage after neoadjuvant treatment, grading and estrogen-receptor status – can be used to identify these patients. The CPS-EG score was validated in 2454 patients with HR-positive/HER2-normal tumours using data obtained from the German neoadjuvant studies' meta-database. Patients who had a score of 3 or higher or a score of 2 and residual node-positive (ypN+) disease show a 3-year iDFS of 77%, despite adequate local therapy and adjuvant endocrine treatment. Cyclin dependent kinases (CDK), a group of serine/threonine kinases, play a key role in regulating cell cycle progression by interacting with specific cyclin proteins in luminal-type tumours. Palbociclib is an oral, highly selective inhibitor of CDK4/6 kinase activity that prevents cellular DNA synthesis by prohibiting progression of the cell cycle from the G1 to S phase by  blocking retinoblastoma (Rb) phosphorylation. Four Preclinical studies identified luminal ER subtype, elevated expression of cyclin D1 and Rb protein, and reduced p16 expression as being associated with sensitivity to palbociclib.

The main objective of PENELOPE-B is to demonstrate that palbociclib provides superior invasive disease-free survival (iDFS) in this high-risk population of patients.

Patients enrolled in PENELOPE-B will be randomly assigned to two different groups. After the surgical procedure to remove the primary breast tumour, patients will receive either:

Standard treatment after surgery for hormone receptor (HR)-positive and HER2 normal breast cancer usually includes at least five years of hormone (endocrine) therapy.

- Group 1 : palbociclib for 13 cycles

- Group 2 : placebo for 13 cycles

All patients will received concomitantly hormone (endocrine) therapy according to standard treatment.

The objective is to recruit 1250 patients.

This study is sponsored and conducted by the German Breast Group (GBG) under the Breast International Group (BIG) umbrella, and in cooperation with the Arbeitsgmeinschaft Gynäkologische Onkologie (AGO) Study Group and The National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation Inc.

The study was launched in late 2013 and is expected to recruit patients through late 2017.  The final overall survival results are anticipated in 2021.

More than 250 hospitals and cancer centres in 11 countries: Australia, Austria, Brazil, France, Germany, Ireland, Italy, Japan, Korea, Spain, UK and US/Canada

Not at present.

Pfizer provides drugs and funding for this study, which is being run according to BIG's Principles of Research Conduct. identifier: NCT01864746