Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 May 10;39(14):1518-1530.
doi: 10.1200/JCO.20.03639. Epub 2021 Apr 1.

Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer-The Penelope-B Trial

Sibylle Loibl  1   2 , Frederik Marmé  3 , Miguel Martin  4   5 , Michael Untch  6 , Hervé Bonnefoi  7 , Sung-Bae Kim  8 , Harry Bear  9   10 , Nicole McCarthy  11 , Mireia Melé Olivé  5   12 , Karen Gelmon  13 , José García-Sáenz  5   14 , Catherine M Kelly  15 , Toralf Reimer  16 , Masakazu Toi  17 , Hope S Rugo  18 , Carsten Denkert  1   19 , Michael Gnant  20   21 , Andreas Makris  22 , Maria Koehler  23 , Cynthia Huang-Bartelett  23 , Maria Jose Lechuga Frean  23 , Marco Colleoni  24 , Gustavo Werutsky  25 , Sabine Seiler  1 , Nicole Burchardi  1 , Valentina Nekljudova  1 , Gunter von Minckwitz  1
Affiliations
Clinical Trial

Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer-The Penelope-B Trial

Sibylle Loibl et al. J Clin Oncol. .

Abstract

Purpose: About one third of patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) will relapse. Thus, additional therapy is needed. Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor demonstrating efficacy in the metastatic setting.

Patients and methods: PENELOPE-B (NCT01864746) is a double-blind, placebo-controlled, phase III study in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer without a pathological complete response after taxane-containing NACT and at high risk of relapse (clinical pathological staging-estrogen receptor grading score ≥ 3 or 2 and ypN+). Patients were randomly assigned (1:1) to receive 13 cycles of palbociclib 125 mg once daily or placebo on days 1-21 in a 28-day cycle in addition to endocrine therapy (ET). Primary end point is invasive disease-free survival (iDFS). Final analysis was planned after 290 iDFS events with a two-sided efficacy boundary P < .0463 because of two interim analyses.

Results: One thousand two hundred fifty patients were randomly assigned. The median age was 49.0 years (range, 19-79), and the majority were ypN+ with Ki-67 ≤ 15%; 59.4% of patients had a clinical pathological staging-estrogen receptor grading score ≥ 3. 50.1% received aromatase inhibitor, and 33% of premenopausal women received a luteinizing hormone releasing hormone analog in addition to either tamoxifen or an aromatase inhibitor. After a median follow-up of 42.8 months (92% complete), 308 events were confirmed. Palbociclib did not improve iDFS versus placebo added to ET-stratified hazard ratio, 0.93 (95% repeated CI, 0.74 to 1.17) and two-sided weighted log-rank test (Cui, Hung, and Wang) P = .525. There was no difference among the subgroups. Most common related serious adverse events were infections and vascular disorders in 113 (9.1%) patients with no difference between the treatment arms. Eight fatal serious adverse events (two palbociclib and six placebo) were reported.

Conclusion: Palbociclib for 1 year in addition to ET did not improve iDFS in women with residual invasive disease after NACT.

PubMed Disclaimer

Conflict of interest statement

Sibylle LoiblHonoraria: Chugai PharmaConsulting or Advisory Role: Pfizer, Roche, Novartis, Seattle Genetics, Celgene, Lilly, AstraZeneca/MedImmune, Bristol-Myers Squibb, Merck KGaA, Abbvie, Amgen, Prime/Medscape, Daiichi Sankyo, Samsung, Puma Biotechnology, Pierre Fabre, Immunomedics, GlaxoSmithKline, EirGenix, BayerResearch Funding: Abbvie, AstraZeneca, Vifor Pharma, Amgen, Celgene, Novartis, Pfizer, Roche, Myriad Genetics, Immunomedics, Seattle Genetics, Daiichi Sankyo, Pierre FabrePatents, Royalties, Other Intellectual Property: Patent Pending EP14153692.0 Frederik MarméHonoraria: Roche/Genentech, Novartis, Pfizer, AstraZeneca, Tesaro, Clovis Oncology, Clovis Oncology, Eisai, Celgene, Genomic Health, PharmaMar, Amgen, CureVac, MSD Oncology, Janssen-Cilag, Immunomedics, Seagen, Myriad GeneticsConsulting or Advisory Role: AstraZeneca, Tesaro, Pfizer, Roche, Novartis, Genomic Health, CureVac, Amgen, Vaccibody, Immunomedics, Celgene, Eisai, Janssen-Cilag, Immunomedics, ImmunomedicsResearch Funding: Roche/Genentech, Novartis, AstraZeneca, Eisai, Tesaro, Tesaro, Tesaro, Clovis Oncology, MSD Oncology, VaccibodyTravel, Accommodations, Expenses: Roche, Roche, Pfizer, Novartis, PharmaMar, AstraZeneca Miguel MartinHonoraria: Roche/Genentech, Lilly, Pfizer, Novartis, Pierre FabreConsulting or Advisory Role: Roche/Genentech, Novartis, Pfizer, Lilly, AstraZeneca, Taiho Pharmaceutical, PharmaMarSpeakers' Bureau: Lilly/ImClone, Lilly/ImClone, Roche/Genentech, Pierre FabreResearch Funding: Novartis, Roche, Puma Biotechnology Michael UntchHonoraria: AstraZeneca, Art tempi, Bristol-Myers Squibb, Celgene, Daiji Sankyo, Roche Pharma AG, Pfizer, Mundipharma, MSD Oncology, Pierre Fabre, Sanofi, Seattle Genetics, AgendiaConsulting or Advisory Role: Amgen, Abbvie, Celgene, Lilly, Mundipharma, Novartis, MSD Oncology, Pfizer, Roche Pharma AG, Agendia, Pierre Fabre, Seattle Genetics Hervé BonnefoiHonoraria: RocheResearch Funding: BayerTravel, Accommodations, Expenses: Roche, Pfizer Sung-Bae KimHonoraria: DAEHWA Pharmaceutical, ISU ABXISConsulting or Advisory Role: Lilly, AstraZeneca, DAEHWA Pharmaceutical, ISU AbxisResearch Funding: Novartis, Dongkook Pharma, Genzyme Harry BearStock and Other Ownership Interests: Abbvie, Pfizer, ViatrisHonoraria: Genomic Health, MerckConsulting or Advisory Role: Merck, RNADxSpeakers' Bureau: Genomic HealthResearch Funding: MerckTravel, Accommodations, Expenses: MerckOpen Payments Link: https://openpaymentsdata.cms.gov/physician/691364 Nicole McCarthyConsulting or Advisory Role: Roche, Pfizer, Novartis, LillyTravel, Accommodations, Expenses: Novartis Karen GelmonHonoraria: AstraZeneca, Merck Sharp & DohmeConsulting or Advisory Role: Pfizer, Novartis, Astrazeneca, Merck, Lilly, Bristol-Myers Squibb, NanoString Technologies, Genomic Health, Janssen Oncology, Roche, MylanResearch Funding: Pfizer, Bristol-Myers Squibb, AstraZeneca, RocheExpert Testimony: Genentech José Angel García-SáenzConsulting or Advisory Role: Novartis, AstraZeneca, Lilly, Seagen, Daiichi Sankyo, Eisai, MSDResearch Funding: AstraZenecaTravel, Accommodations, Expenses: Roche, Novartis Catherine M. KellyHonoraria: Roche, Pfizer, Novartis, MSD Oncology, Exact Sciences, Daiichi Sankyo Europe GmbHTravel, Accommodations, Expenses: Roche, pfizer Toralf ReimerConsulting or Advisory Role: PfizerResearch Funding: Else Kröner-Fresenius-Stiftung, German Cancer AidOther Relationship: Pfizer Masakazu ToiHonoraria: Novartis, TAKEDA, AstraZeneca, Eisai, Chugai Pharma, Taiho Pharmaceutical, Daiichi Sankyo, Yakult Pharmaceutical, Shimadzu, Pfizer, Konica Minolta, Lilly, Kyowa Kirin, Devicore medical Japan, Exact Sciences, Nippon KayakuConsulting or Advisory Role: Daiichi Sankyo, Kyowa Kirin, Bertis, Athenex, Bristol-Myers Squibb, Kansai Medical Net, Terumo, Luxonus, Luxonus, AstraZeneca, LillySpeakers' Bureau: Pfizer, AstraZeneca, Lilly, Daiichi SankyoResearch Funding: Taiho Pharmaceutical, Chugai Pharma, Shimadzu, Astellas Pharma, AFI technology, Japan Breast Cancer Research Group, Pfizer, Eisai, Daiichi Sankyo, AstraZeneca, Ono Pharmaceutical, Nippon Kayaku, Kyoto Breast cancer Research NetworkPatents, Royalties, Other Intellectual Property: JP 2017-143763 WO2017/131162A1, PCT/JP2016/004374Travel, Accommodations, Expenses: Eisai, TakedaOther Relationship: Japan Breast Cancer Research Group, Kyoto Breast Cancer Research Network, Organization for Oncology and Translational Research Hope S. RugoConsulting or Advisory Role: Samsung, Celltrion, Puma BiotechnologyResearch Funding: Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Lilly, Genentech, Merck, Immunomedics, Odonate Therapeutics, Daiichi Sankyo, Seattle GeneticsTravel, Accommodations, Expenses: Pfizer, Novartis, Macrogenics, Mylan, Daiichi Sankyo, AstraZeneca SpainOpen Payments Link: https://openpaymentsdata.cms.gov/summary Carsten DenkertStock and Other Ownership Interests: Sividon Diagnostics (now Myriad)Honoraria: Novartis, RocheConsulting or Advisory Role: MSD Oncology, Daiichi Sankyo, Molecular HealthResearch Funding: Myriad GeneticsPatents, Royalties, Other Intellectual Property: VMScope digital pathology software, Patent application: EP18209672—cancer immunotherapy, Patent application EP20150702464—therapy response, Patent application EP20150702464—therapy responseTravel, Accommodations, Expenses: Roche Michael GnantEmployment: SandozHonoraria: Celgene, Roche, Novartis, AstraZeneca, Amgen, NanoString Technologies, Lilly, Medison, PfizerConsulting or Advisory Role: AstraZeneca, LillyTravel, Accommodations, Expenses: AstraZeneca, Pfizer, Amgen, Ipsen, Lilly, Medtronic, Roche/Genentech Andreas MakrisHonoraria: NanoString Technologies, Lilly, Roche, PfizerConsulting or Advisory Role: Roche, Lilly, PfizerSpeakers' Bureau: NanoString Technologies, Pfizer, Lilly, RocheTravel, Accommodations, Expenses: Roche Maria KoehlerEmployment: Bicycle Therapeutics, Repare TherapeuticsStock and Other Ownership Interests: Pfizer, Agios, Amgen, Merck, Gilead SciencesHonoraria: GLG, AtheneumConsulting or Advisory Role: ERVAXX, Lilly Asia Ventures Cynthia Huang-BartelettEmployment: Pfizer, Merck, AstraZenecaStock and Other Ownership Interests: Pfizer, AstraZeneca Maria Jose Lechuga FreanEmployment: PfizerStock and Other Ownership Interests: Pfizer Sabine SeilerStock and Other Ownership Interests: RocheConsulting or Advisory Role: Mundipharma, AmgenTravel, Accommodations, Expenses: Novartis Gunter von MinckwitzStock and Other Ownership Interests: CARA GmbHNo other potential conflicts of interest were reported.

Comment in

Publication types

Associated data

LinkOut - more resources