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Clinical Trial
. 2021 Feb;21(1):80-91.e7.
doi: 10.1016/j.clbc.2020.09.014. Epub 2020 Oct 6.

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

Arlene Chan  1 , Beverly Moy  2 , Janine Mansi  3 , Bent Ejlertsen  4 , Frankie Ann Holmes  5 , Stephen Chia  6 , Hiroji Iwata  7 , Michael Gnant  8 , Sibylle Loibl  9 , Carlos H Barrios  10 , Isil Somali  11 , Snezhana Smichkoska  12 , Noelia Martinez  13 , Mirta Garcia Alonso  14 , John S Link  15 , Ingrid A Mayer  16 , Søren Cold  17 , Serafin Morales Murillo  18 , Francis Senecal  19 , Kenichi Inoue  20 , Manuel Ruiz-Borrego  21 , Rina Hui  22 , Neelima Denduluri  23 , Debra Patt  24 , Hope S Rugo  25 , Stephen R D Johnston  26 , Richard Bryce  27 , Bo Zhang  27 , Feng Xu  27 , Alvin Wong  27 , Miguel Martin  28 ; ExteNET Study Group
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Free article
Clinical Trial

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

Arlene Chan et al. Clin Breast Cancer. 2021 Feb.
Free article

Abstract

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.

Keywords: Adjuvant therapy; Disease-free survival; Distant disease-free survival; Neoadjuvant therapy; Overall survival.

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