1. Overall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trial.
- Author
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Holmes, Frankie A., Moy, Beverly, Delaloge, Suzette, Chia, Stephen K.L., Ejlertsen, Bent, Mansi, Janine, Iwata, Hiroji, Gnant, Michael, Buyse, Marc, Barrios, Carlos H., Silovski, Tajana, Šeparović, Robert, Bashford, Anna, Zotano, Angel Guerrero, Denduluri, Neelima, Patt, Debra, Gokmen, Erhan, Gore, Ira, Smith II, John W., and Loibl, Sibylle
- Subjects
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BREAST cancer prognosis , *ADJUVANT chemotherapy , *CONFIDENCE intervals , *TRASTUZUMAB , *ANTINEOPLASTIC agents , *PROTEIN-tyrosine kinase inhibitors , *TREATMENT effectiveness , *TUMOR classification , *RANDOMIZED controlled trials , *PLACEBOS , *COMPARATIVE studies , *PRE-tests & post-tests , *BLIND experiment , *DESCRIPTIVE statistics , *STATISTICAL sampling , *BREAST tumors , *WOMEN'S health - Abstract
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. 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. 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). 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. • Neratinib improves iDFS after trastuzumab in early HER2+ breast cancer. • We report the final analysis of overall survival from the phase 3 ExteNET trial. • At 8 years' follow-up, OS in the ITT population was similar with neratinib vs placebo. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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