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

被引：143

作者：

Chan, Arlene ^{[1
,2
]}

Moy, Beverly ^{[3
]}

Mansi, Janine ^{[4
,5
]}

Ejlertsen, Bent ^{[6
]}

Holmes, Frankie Ann ^{[7
]}

Chia, Stephen ^{[8
]}

Iwata, Hiroji ^{[9
]}

Gnant, Michael ^{[10
]}

Loibl, Sibylle ^{[11
]}

Barrios, Carlos H. ^{[12
]}

Somali, Isil ^{[13
]}

Smichkoska, Snezhana ^{[14
]}

Martinez, Noelia ^{[15
]}

Alonso, Mirta Garcia ^{[16
]}

Link, John S. ^{[17
]}

Mayer, Ingrid A. ^{[18
]}

Cold, Soren ^{[19
]}

Murillo, Serafin Morales ^{[20
]}

Senecal, Francis ^{[21
]}

Inoue, Kenichi ^{[22
]}

Ruiz-Borrego, Manuel ^{[23
]}

Hui, Rina ^{[24
,25
]}

Denduluri, Neelima ^{[26
]}

Patt, Debra ^{[27
]}

Rugo, Hope S. ^{[28
]}

Johnston, Stephen R. D. ^{[29
]}

Bryce, Richard ^{[30
]}

Zhang, Bo ^{[30
]}

Xu, Feng ^{[30
]}

Wong, Alvin ^{[30
]}

Martin, Miguel ^{[31
]}

机构：

[1] Breast Canc Res Ctr WA, Breast Clin Trials Unit, Perth, WA, Australia

[2] Curtin Univ, Perth, WA, Australia

[3] Massachusetts Gen Hosp Canc Ctr, Breast Oncol Program, Boston, MA USA

[4] Guys & St Thomas Hosp NHS Fdn Trust, Oncol & Haematol Clin Trials, London, England

[5] Kings Coll London, Biomed Res Ctr, London, England

[6] Rigshosp, Dept Oncol, Copenhagen, Denmark

[7] Texas Oncol US Oncol Res, Houston, TX USA

[8] BC Canc Agcy, Med Oncol, Vancouver, BC, Canada

[9] Aichi Canc Ctr, Clin Oncol, Chikusa Ku, Nagoya, Aichi, Japan

[10] Med Univ Vienna, Comprehens Canc Ctr, Vienna, Austria

[11] Ctr Hematol & Oncol Bethanien, Frankfurt, Germany

[12] Pontificia Univ Catolica Rio Grande do Sul, Hosp Sao Lucas, Ctr Pesquisa Oncol, Porto Alegre, RS, Brazil

[13] Dokuz Eylul Univ, Dept Oncol, Tip Fak Hastanesi, Tibbi Onkol Anabilim Dali Mithatpasa, Izmir, Turkey

[14] Ss Cyril & Methodius Univ Skopje, Univ Clin Radiotherapy & Oncol, Skopje, North Macedonia

[15] Hosp Univ Ramon y Cajal, Dept Med Oncol, Madrid, Spain

[16] Hosp Univ Nuestra Senora de la Candelaria, Oncol Med, Ctra Rosario, San Cristobal la Laguna, Canarias, Spain

[17] Breastlink Med Grp Inc, Santa Ana, CA USA

[18] Vanderbilt Ingram Canc Ctr, Div Hematol Oncol, Breast Canc Program, Nashville, TN USA

[19] Odense Univ Hosp, Onkol Afdeling R, Odense, Denmark

[20] Hosp Univ Arnau Vilanova Serv Oncol Med & Hematol, Lleida, Spain

[21] Northwest Med Specialties PLLC, Phys Med Ctr, Tacoma, WA USA

[22] Saitama Canc Ctr, Breast Oncol, Kita Adachi, Japan

[23] Hosp Univ Virgen del Rocio, Oncol, Seville, Spain

[24] Westmead Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia

[25] Univ Sydney, Sydney, NSW, Australia

[26] Virginia Canc Specialists, Arlington, VA USA

[27] Texas Oncol Round Rock, Austin, TX USA

[28] Univ Calif San Francisco, Dept Med Hematol Oncol, Comprehens Canc Ctr, San Francisco, CA 94143 USA

[29] Royal Marsden NHS Fdn Trust, Breast Unit, London, England

[30] Puma Biotechnol Inc, Los Angeles, CA USA

[31] Univ Complutense, Inst Invest Sanitaria Gregorio Maranon, Med Oncol Serv, GEICAM,CIBERONC, Madrid, Spain

来源：

CLINICAL BREAST CANCER | 2021年 / 21卷 / 01期

关键词：

Adjuvant therapy; Disease-free survival; Distant disease-free survival; Neoadjuvant therapy; Overall survival; PLUS ADJUVANT CHEMOTHERAPY; DOUBLE-BLIND; TRASTUZUMAB; THERAPY; MULTICENTER; SURVIVAL; OUTCOMES;

D O I：

10.1016/j.clbc.2020.09.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In the patient population with early-stage human epidermal growth factor receptor 2-positive/hormone receptor-positive breast cancer who initiate neratinib within 1 year of trastuzumab-based therapy, the absolute 5-year invasive disease-free survival benefit versus placebo is 5.1%, and absolute 8-year overall survival benefit is 2.1%. Among those with residual disease after neoadjuvant therapy (non-pathologic complete response), absolute gains with neratinib are 7.4% and 9.1%, respectively. 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 (HRthorn) early-stage breast cancer (eBC). Patients and Methods: ExteNET was a multicenter, randomized, double-blind, phase III trial of 2840 patients with HER2thorn 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. (C) 2020 The Author(s). Published by Elsevier Inc.

引用

页码：80 / +

页数：19

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