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Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial

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  • Arlene Chan
  • Beverly Moy
  • Janine Mansi
  • Bent Ejlertsen
  • Frankie Ann Holmes
  • Stephen Chia
  • Hiroji Iwata
  • Michael Gnant
  • Sibylle Loibl
  • Carlos H Barrios
  • Isil Somali
  • Snezhana Smichkoska
  • Noelia Martinez
  • Mirta Garcia Alonso
  • John S Link
  • Ingrid A Mayer
  • Søren Cold
  • Serafin Morales Murillo
  • Francis Senecal
  • Kenichi Inoue
  • Manuel Ruiz-Borrego
  • Rina Hui
  • Neelima Denduluri
  • Debra Patt
  • Hope S Rugo
  • Stephen R D Johnston
  • Richard Bryce
  • Bo Zhang
  • Feng Xu
  • Alvin Wong
  • Miguel Martin
  • ExteNET Study Group
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BACKGROUND: The ExteNET trial demonstrated improved invasive disease-free survival (iDFS) with neratinib, an irreversible pan-HER tyrosine kinase inhibitor, versus placebo in patients with human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-positive (HR+) early-stage breast cancer (eBC).

PATIENTS AND METHODS: ExteNET was a multicenter, randomized, double-blind, phase III trial of 2840 patients with HER2+ eBC after neoadjuvant/adjuvant trastuzumab-based therapy. Patients were stratified by HR status and randomly assigned 1-year oral neratinib 240 mg/day or placebo. The primary endpoint was iDFS. Descriptive analyses were performed in patients with HR+ eBC who initiated treatment ≤ 1 year (HR+/≤ 1-year) and > 1 year (HR+/> 1-year) post-trastuzumab.

RESULTS: HR+/≤ 1-year and HR+/> 1-year populations comprised 1334 (neratinib, n = 670; placebo, n = 664) and 297 (neratinib, n = 146; placebo, n = 151) patients, respectively. Absolute iDFS benefits at 5 years were 5.1% in HR+/≤ 1-year (hazard ratio, 0.58; 95% confidence interval [CI], 0.41-0.82) and 1.3% in HR+/>1-year (hazard ratio, 0.74; 95% CI, 0.29-1.84). In HR+/≤ 1-year, neratinib was associated with a numerical improvement in overall survival (OS) at 8 years (absolute benefit, 2.1%; hazard ratio, 0.79; 95% CI, 0.55-1.13). Of 354 patients in the HR+/≤ 1-year group who received neoadjuvant therapy, 295 had residual disease, and results showed absolute benefits of 7.4% at 5-year iDFS (hazard ratio, 0.60; 95% CI, 0.33-1.07) and 9.1% at 8-year OS (hazard ratio, 0.47; 95% CI, 0.23-0.92). There were fewer central nervous system events with neratinib. Adverse events were similar to those previously reported.

CONCLUSION: Neratinib significantly improved iDFS in the HER2+/HR+/≤ 1-year population, and a similar trend was observed in patients with residual disease following neoadjuvant treatment. Numerical improvements in central nervous system events and OS were consistent with iDFS benefits and suggest long-term benefit for neratinib in this population.

Original languageEnglish
JournalBreast Cancer: Basic and Clinical Research
Issue number1
Pages (from-to)80-91.e7
Publication statusPublished - Feb 2021

ID: 61368745