Institut za onkologiju i radiologiju Srbije / Institute for Oncology and Radiology of Serbia
Published February 10, 2023 | Version v.1
Journal article Open

Overall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trial

Creators

  • 1. a Texas Oncology, P.A., US Oncology Research, Houston, TX, USA
  • 2. Massachusetts General Hospital Cancer Center, Boston, MA, USA
  • 3. Institut Gustave Roussy, Villejuif, France
  • 4. BC Cancer Agency, Vancouver, BC, Canada
  • 5. Rigshospitalet, Copenhagen, Denmark
  • 6. Guy's and St Thomas Hospital NHS Foundation Trust and Biomedical Research Centre, King's College, London, United Kingdom
  • 7. Aichi Cancer Center, Chikusa-ku, Nagoya, Japan
  • 8. Comprehensive Cancer Centre, Medical University of Vienna, Vienna, Austria
  • 9. International Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium
  • 10. Hospital Sa˜o Lucas, PUCRS, Porto Alegre, Brazil
  • 11. Department of Oncology, UHC Zagreb, Zagreb, Croatia
  • 12. University Hospital for Tumors, University Hospital Center "Sestre Milosrdnice", Zagreb, Croatia
  • 13. Auckland Hospital, Auckland, New Zealand
  • 14. Instituto Valenciano de Oncologia, Valencia, Spain
  • 15. Virginia Cancer Specialists, US Oncology Research, Arlington, VA, USA
  • 16. Texas Oncology e Round Rock, US Oncology Research, Austin, TX, USA
  • 17. Ege University Faculty of Medicine, Izmir, Turkey
  • 18. Alabama Oncology, Birmingham, AL, USA
  • 19. Northwest Cancer Specialists, P.C., US Oncology Research, Vancouver, VA, USA
  • 20. Center for Hematology and Oncology Bethanien, Frankfurt, Germany and German Breast Group, Neu-Isenburg, Germany
  • 21. Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • 22. Daily Chemotherapy Hospital, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
  • 23. Masaryk Memorial Cancer Institute, Brno, Czech Republic
  • 24. Puma Biotechnology Inc., Los Angeles, CA, USA
  • 25. Instituto de Investigacio´n Sanitaria Gregorio Maran˜o´n, CIBERONC, GEICAM, Universidad Complutense, Madrid, Spain
  • 26. Breast Cancer Research Centre-WA & Curtin University, Perth, Australia

Description

Abstract.  Background: ExteNET showed that neratinib, an irreversible pan-HER tyrosine kinase inhibitor, given for 1 year after trastuzumab-based therapy significantly improved invasive disease-free survival in women with early-stage HER2-positive breast cancer. We report the final analysis of overall survival in ExteNET. Methods: In this international, randomised, double-blind, placebo-controlled, phase 3 trial, women aged 18 years or older with stage 1e3c (amended to stage 2e3c) HER2-positive breast
cancer who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab were eligible. Patients were randomly assigned to oral neratinib 240 mg/day or placebo for 1 year. Randomisation was stratified according to hormone receptor (HR) status (HR-positive vs. HR-negative), nodal status (0, 1e3 or 4þ), and trastuzumab regimen (sequentially vs. concurrently with chemotherapy). Overall survival was analysed by intention to treat. ExteNET is registered (Clinicaltrials.gov: NCT00878709) and is complete.
Results: Between July 9, 2009, and October 24, 2011, 2840 women received neratinib (n Z 1420) or placebo (n Z 1420). After a median follow-up of 8.1 (IQR, 7.0e8.8) years, 127 patients (8.9%) in the neratinib group and 137 patients (9.6%) in the placebo group in the intention-to-treat population had died. Eight-year overall survival rates were 90.1% (95% CI 88.3e91.6) with neratinib and 90.2% (95% CI 88.4e91.7) with placebo (stratified hazard ratio 0.95; 95% CI 0.75e1.21; p Z 0.6914).
Conclusions: Overall survival in the extended adjuvant setting was comparable for neratinib and placebo after a median follow-up of 8.1 years in women with early-stage HER2- positive breast cancer.

Notes

Authors thanks the Independent Data Monitoring Committee, study investigators, research staff, clinical research organizations, and other vendors, as well as the patients who participated in the ExteNET trial. We also acknowledge the contributions of Janine Lu, Judith Bebchuk and Bethann Hromatka of Puma Biotechnology Inc.; Richard Bryce, Feng Xu, Yan Yan and Bo Zhang (former employees of Puma Biotechnology Inc.); and Harriet Lamb and Lee Miller of Miller Medical Communications Ltd.

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Additional details

Related works

Is documented by
36898233 (PMID)
Is part of
0959-8049 (ISSN)
Is supplemented by
10.1016/j.ejca.2023.02.002. (DOI)