A Study of Palbociclib in Addition to Standard Endocrine Treatment in Hormone Receptor Positive Her2 Normal Patients With Residual Disease After Neoadjuvant Chemotherapy and Surgery

Summary

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.

Timeline

Start

2013-10-30

Primary completion

2020-08-24

Completion

2020-12-21

Publications

• Background Mittendorf EA, Jeruss JS, Tucker SL, Kolli A, Newman LA, Gonzalez-Angulo AM, Buchholz TA, Sahin AA, Cormier JN, Buzdar AU, Hortobagyi GN, Hunt KK. Validation of a novel staging system for disease-specific survival in patients with breast cancer treated with neoadjuvant chemotherapy. J Clin Oncol. 2011 May 20;29(15):1956-62. doi: 10.1200/JCO.2010.31.8469. Epub 2011 Apr 11.
• Background Musgrove EA, Caldon CE, Barraclough J, Stone A, Sutherland RL. Cyclin D as a therapeutic target in cancer. Nat Rev Cancer. 2011 Jul 7;11(8):558-72. doi: 10.1038/nrc3090.
• Background ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012 Sep 6;489(7414):57-74. doi: 10.1038/nature11247.
• Background Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, Ginther C, Atefi M, Chen I, Fowst C, Los G, Slamon DJ. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11(5):R77. doi: 10.1186/bcr2419.
• Background Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007 Oct 1;25(28):4414-22. doi: 10.1200/JCO.2007.10.6823. Epub 2007 Sep 4.
• Background Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005 Feb 2;97(3):188-94. doi: 10.1093/jnci/dji021.
• Background von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J, Jackisch C, Kaufmann M, Konecny GE, Denkert C, Nekljudova V, Mehta K, Loibl S. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012 May 20;30(15):1796-804. doi: 10.1200/JCO.2011.38.8595. Epub 2012 Apr 16.
• Results Loibl S, Marme F, Martin M, Untch M, Bonnefoi H, Kim SB, Bear H, McCarthy N, Mele Olive M, Gelmon K, Garcia-Saenz J, Kelly CM, Reimer T, Toi M, Rugo HS, Denkert C, Gnant M, Makris A, Koehler M, Huang-Bartelett C, Lechuga Frean MJ, Colleoni M, Werutsky G, Seiler S, Burchardi N, Nekljudova V, von Minckwitz G. Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer-The Penelope-B Trial. J Clin Oncol. 2021 May 10;39(14):1518-1530. doi: 10.1200/JCO.20.03639. Epub 2021 Apr 1.
• Hahnen E, Hauke J, Gelmon K, Marme F, Ernst C, Martin M, Untch M, Bonnefoi H, Knudsen E, Im SA, DeMichele A, Van't Veer L, Kim SB, Bear H, McCarthy N, Rhiem K, Turner N, Witkiewicz A, Rojo F, Filipits M, Martin LA, Fasching PA, Schem C, Becker K, Garcia-Saenz JA, Kelly CM, Reimer T, Toi M, Rugo HS, Denkert C, Gnant M, Makris A, Liu Y, Valota O, Felder B, Weber K, Nekljudova V, Loibl S. BRCA1/2 and Other Predisposition Genes in High-Risk Hormone Receptor+/Human Epidermal Growth Factor Receptor 2- Breast Cancer Treated With Endocrine Therapy With or Without Palbociclib: A Secondary PENELOPE-B Study Analysis. JCO Precis Oncol. 2025 Apr;9:e2400742. doi: 10.1200/PO-24-00742. Epub 2025 Apr 10.

Drugs

Indications