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 1-3c (amended to stage 2-3c) 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, 1-3 or 4+), 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 = 1420) or placebo (n = 1420). After a median follow-up of 8.1 (IQR, 7.0-8.8) 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 88.3-91.6) with neratinib and 90.2% (95% CI 88.4-91.7) with placebo (stratified hazard ratio 0.95; 95% CI 0.75-1.21; p = 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.

Aichi Cancer Center Chikusa ku Nagoya Japan

Alabama Oncology Birmingham AL USA

Auckland Hospital Auckland New Zealand

BC Cancer Agency Vancouver BC Canada

Breast Cancer Research Centre WA and Curtin University Perth Australia

Center for Hematology and Oncology Bethanien Frankfurt Germany and German Breast Group Neu Isenburg Germany

Comprehensive Cancer Centre Medical University of Vienna Vienna Austria

Daily Chemotherapy Hospital Institute for Oncology and Radiology of Serbia Belgrade Serbia

Department of Breast and Endocrine Surgery Nagoya University Graduate School of Medicine Nagoya Japan

Department of Oncology UHC Zagreb Zagreb Croatia

Ege University Faculty of Medicine Izmir Turkey

Guy's and St Thomas Hospital NHS Foundation Trust and Biomedical Research Centre King's College London United Kingdom

Hospital São Lucas PUCRS Porto Alegre Brazil

Institut Gustave Roussy Villejuif France

Instituto de Investigación Sanitaria Gregorio Marañón CIBERONC GEICAM Universidad Complutense Madrid Spain

Instituto Valenciano de Oncologia València Spain

International Drug Development Institute Louvain la Neuve Belgium

Masaryk Memorial Cancer Institute Brno Czech Republic

Massachusetts General Hospital Cancer Center Boston MA USA

Northwest Cancer Specialists P C US Oncology Research Vancouver VA USA

Puma Biotechnology Inc Los Angeles CA USA

Rigshospitalet Copenhagen Denmark

Texas Oncology P A US Oncology Research Houston TX USA

Texas Oncology Round Rock US Oncology Research Austin TX USA

University Hospital for Tumors University Hospital Center Sestre Milosrdnice Zagreb Croatia

Virginia Cancer Specialists US Oncology Research Arlington VA USA

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ClinicalTrials.gov
NCT00878709