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

Background: ExteNET showed that neratinib, an irreversible pan-HER tyrosine ki-nase inhibitor, given for 1 year after trastuzumab-based therapy significantly improved inva-sive 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 thorn ), and trastuzumab regimen (sequentially vs. concur-rently 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 haz-ard 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.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

ExteNET study showed that neratinib significantly improved invasive disease-free survival in women with early-stage HER2-positive breast cancer compared to placebo after 1 year of treatment with trastuzumab-based therapy. The final analysis revealed that overall survival rates were comparable between neratinib and placebo in the extended adjuvant setting.