Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer-the penelope-B trial

Sibylle Loibl, Frederik Marmé, Miguel Martin, Michael Untch, Hervé Bonnefoi, Sung Bae Kim, Harry Bear, Nicole McCarthy, Mireia Melé Olivé, Karen Gelmon, José García-Sáenz, Catherine M. Kelly, Toralf Reimer, Masakazu Toi, Hope S. Rugo, Carsten Denkert, Michael Gnant, Andreas Makris, Maria Koehler, Cynthia Huang-BartelettMaria Jose Lechuga Frean, Marco Colleoni, Gustavo Werutsky, Sabine Seiler, Nicole Burchardi, Valentina Nekljudova, Gunter von Minckwitz

Research output: Contribution to journalArticlepeer-review

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 ypN1). 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 ypN1 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 5.525. 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.

Original languageEnglish
Pages (from-to)1518-1530
Number of pages13
JournalJournal of Clinical Oncology
Volume39
Issue number14
DOIs
Publication statusPublished - May 10 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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