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

Arlene Chan; Beverly Moy; Janine Mansi; Bent Ejlertsen; Frankie Ann Holmes; Stephen Chia; Hiroji Iwata; Michael Gnant; Sibylle Loibl; Carlos H Barrios; Isil Somali; Snezhana Smichkoska; Noelia Martinez; Mirta Garcia Alonso; John S Link; Ingrid A Mayer; Søren Cold; Serafin Morales Murillo; Francis Senecal; Kenichi Inoue; Manuel Ruiz-Borrego; Rina Hui; Neelima Denduluri; Debra Patt; Hope S Rugo; Stephen R D Johnston; Richard Bryce; Bo Zhang; Feng Xu; Alvin Wong; Miguel Martin; ExteNET Study Group

doi:10.1016/j.clbc.2020.09.014

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

Arlene Chan^*, Beverly Moy, Janine Mansi, Bent Ejlertsen, Frankie Ann Holmes, Stephen Chia, Hiroji Iwata, Michael Gnant, Sibylle Loibl, Carlos H Barrios, Isil Somali, Snezhana Smichkoska, Noelia Martinez, Mirta Garcia Alonso, John S Link, Ingrid A Mayer, Søren Cold, Serafin Morales Murillo, Francis Senecal, Kenichi InoueManuel Ruiz-Borrego, Rina Hui, Neelima Denduluri, Debra Patt, Hope S Rugo, Stephen R D Johnston, Richard Bryce, Bo Zhang, Feng Xu, Alvin Wong, Miguel Martin, ExteNET Study Group

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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.

Originalsprog	Engelsk
Tidsskrift	Breast Cancer: Basic and Clinical Research
Vol/bind	21
Udgave nummer	1
Sider (fra-til)	80-91.e7
ISSN	1178-2234
DOI	https://doi.org/10.1016/j.clbc.2020.09.014
Status	Udgivet - feb. 2021

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10.1016/j.clbc.2020.09.014

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Chan, A., Moy, B., Mansi, J., Ejlertsen, B., Holmes, F. A., Chia, S., Iwata, H., Gnant, M., Loibl, S., Barrios, C. H., Somali, I., Smichkoska, S., Martinez, N., Alonso, M. G., Link, J. S., Mayer, I. A., Cold, S., Murillo, S. M., Senecal, F., ... ExteNET Study Group (2021). Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial. Breast Cancer: Basic and Clinical Research, 21(1), 80-91.e7. https://doi.org/10.1016/j.clbc.2020.09.014

Chan, A, Moy, B, Mansi, J, Ejlertsen, B, Holmes, FA, Chia, S, Iwata, H, Gnant, M, Loibl, S, Barrios, CH, Somali, I, Smichkoska, S, Martinez, N, Alonso, MG, Link, JS, Mayer, IA, Cold, S, Murillo, SM, Senecal, F, Inoue, K, Ruiz-Borrego, M, Hui, R, Denduluri, N, Patt, D, Rugo, HS, Johnston, SRD, Bryce, R, Zhang, B, Xu, F, Wong, A, Martin, M & ExteNET Study Group 2021, 'Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial', Breast Cancer: Basic and Clinical Research, bind 21, nr. 1, s. 80-91.e7. https://doi.org/10.1016/j.clbc.2020.09.014

@article{25787e48219446dda0c5f667cf7676ae,

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

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",

author = "Arlene Chan and Beverly Moy and Janine Mansi and Bent Ejlertsen and Holmes, {Frankie Ann} and Stephen Chia and Hiroji Iwata and Michael Gnant and Sibylle Loibl and Barrios, {Carlos H} and Isil Somali and Snezhana Smichkoska and Noelia Martinez and Alonso, {Mirta Garcia} and Link, {John S} and Mayer, {Ingrid A} and S{\o}ren Cold and Murillo, {Serafin Morales} and Francis Senecal and Kenichi Inoue and Manuel Ruiz-Borrego and Rina Hui and Neelima Denduluri and Debra Patt and Rugo, {Hope S} and Johnston, {Stephen R D} and Richard Bryce and Bo Zhang and Feng Xu and Alvin Wong and Miguel Martin and {ExteNET Study Group}",

year = "2021",

month = feb,

doi = "10.1016/j.clbc.2020.09.014",

language = "English",

volume = "21",

pages = "80--91.e7",

journal = "Breast Cancer: Basic and Clinical Research",

issn = "1178-2234",

publisher = "Libertas Academica Ltd",

number = "1",

}

TY - JOUR

T1 - Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial

AU - Chan, Arlene

AU - Moy, Beverly

AU - Mansi, Janine

AU - Ejlertsen, Bent

AU - Holmes, Frankie Ann

AU - Chia, Stephen

AU - Iwata, Hiroji

AU - Gnant, Michael

AU - Loibl, Sibylle

AU - Barrios, Carlos H

AU - Somali, Isil

AU - Smichkoska, Snezhana

AU - Martinez, Noelia

AU - Alonso, Mirta Garcia

AU - Link, John S

AU - Mayer, Ingrid A

AU - Cold, Søren

AU - Murillo, Serafin Morales

AU - Senecal, Francis

AU - Inoue, Kenichi

AU - Ruiz-Borrego, Manuel

AU - Hui, Rina

AU - Denduluri, Neelima

AU - Patt, Debra

AU - Rugo, Hope S

AU - Johnston, Stephen R D

AU - Bryce, Richard

AU - Zhang, Bo

AU - Xu, Feng

AU - Wong, Alvin

AU - Martin, Miguel

AU - ExteNET Study Group

PY - 2021/2

Y1 - 2021/2

N2 - 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.

AB - 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.

KW - Adjuvant therapy

KW - Disease-free survival

KW - Distant disease-free survival

KW - Neoadjuvant therapy

KW - Overall survival

UR - http://www.scopus.com/inward/record.url?scp=85095826918&partnerID=8YFLogxK

U2 - 10.1016/j.clbc.2020.09.014

DO - 10.1016/j.clbc.2020.09.014

M3 - Journal article

C2 - 33183970

SN - 1178-2234

VL - 21

SP - 80-91.e7

JO - Breast Cancer: Basic and Clinical Research

JF - Breast Cancer: Basic and Clinical Research

IS - 1

ER -

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

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