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

Source: https://onco.cc/key-papers/paper-penelope-b-j-clin-oncol-2021/  
OnCo record `paper-penelope-b-j-clin-oncol-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the PENELOPE-B trial registered as NCT01864746, in Journal of Clinical Oncology (2021), chosen as the most cited paper whose own text cites the registry id.

## Summary

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.

Indexed on Europe PMC as PubMed record 33793299 (DOI 10.1200/jco.20.03639). Its abstract cites the registry id NCT01864746, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Journal of Clinical Oncology
- Year: 2021
- DOI: 10.1200/jco.20.03639
- Authors: Loibl S, Marmé F, Martin M, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT01864746 with the most citations, so it is the natural first reading for anyone following the PENELOPE-B trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- J Clin Oncol 2021: https://doi.org/10.1200/jco.20.03639
- PubMed: https://pubmed.ncbi.nlm.nih.gov/33793299/
- Europe PMC: https://europepmc.org/article/MED/33793299
- ClinicalTrials.gov NCT01864746: https://clinicaltrials.gov/study/NCT01864746

## Connected records

- trials: [PENELOPE-B](https://onco.cc/trials/penelope-b/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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