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

被引：165

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

共 31 条

[1] Safety and Efficacy of T-DM1 Plus Neratinib in Patients With Metastatic HER2-Positive Breast Cancer: NSABP Foundation Trial FB-10 [J].

Abraham, Jame ;

Montero, Albert J. ;

Jankowitz, Rachel C. ;

Salkeni, Mohamad Adham ;

Beumer, Jan H. ;

Kiesel, Brian F. ;

Piette, Fanny ;

Adamson, Laura M. ;

Nagy, Rebecca J. ;

Lanman, Richard B. ;

Sperinde, Jeff ;

Huang, Weidong ;

Allegra, Carmen J. ;

Srinivasan, Ashok ;

Wang, Ying ;

Pogue-Geile, Katherine L. ;

Lucas, Peter C. ;

Jacobs, Samuel A. .

JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (29) :2601-+

[2]

[Anonymous], 2020, NERLYNX NERATINIB TA

[3]

[Anonymous], 2020, NERLYNX NERATINIB 40

[4] Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer The NEfERT-T Randomized Clinical Trial [J].

Awada, Ahmad ;

Colomer, Ramon ;

Inoue, Kenichi ;

Bondarenko, Igor ;

Badwe, Rajendra A. ;

Demetriou, Georgia ;

Lee, Soo-Chin ;

Mehta, Ajay O. ;

Kim, Sung-Bae ;

Bachelot, Thomas ;

Goswami, Chanchal ;

Deo, Suryanarayan ;

Bose, Ron ;

Wong, Alvin ;

Xu, Feng ;

Yao, Bin ;

Bryce, Richard ;

Carey, Lisa A. .

JAMA ONCOLOGY, 2016, 2 (12) :1557-1564

[5] Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial [J].

Barcenas, C. H. ;

Hurvitz, S. A. ;

Di Palma, J. A. ;

Bose, R. ;

Chien, A. J. ;

Iannotti, N. ;

Marx, G. ;

Brufsky, A. ;

Litvak, A. ;

Ibrahim, E. ;

Alvarez, R. H. ;

Ruiz-Borrego, M. ;

Chan, N. ;

Manalo, Y. ;

Kellum, A. ;

Trudeau, M. ;

Thirlwell, M. ;

Saenz, J. Garcia ;

Hunt, D. ;

Bryce, R. ;

McCulloch, L. ;

Rugo, H. S. ;

Tripathy, D. ;

Chan, A. .

ANNALS OF ONCOLOGY, 2020, 31 (09) :1223-1230

[6] Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes A Meta-Analysis [J].

Broglio, Kristine R. ;

Quintana, Melanie ;

Foster, Margaret ;

Olinger, Melissa ;

McGlothlin, Anna ;

Berry, Scott M. ;

Boileau, Jean-Francois ;

Brezden-Masley, Christine ;

Chia, Stephen ;

Dent, Susan ;

Gelmon, Karen ;

Paterson, Alexander ;

Rayson, Daniel ;

Berry, Donald A. .

JAMA ONCOLOGY, 2016, 2 (06) :751-760

[7] Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial [J].

Chan, Arlene ;

Delaloge, Suzette ;

Holmes, Frankie A. ;

Moy, Beverly ;

Iwata, Hiroji ;

Harvey, Vernon J. ;

Robert, Nicholas J. ;

Silovski, Tajana ;

Gokmen, Erhan ;

von Minckwitz, Gunter ;

Ejlertsen, Bent ;

Chia, Stephen K. L. ;

Mansi, Janine ;

Barrios, Carlos H. ;

Gnant, Michael ;

Buyse, Marc ;

Gore, Ira ;

Smith, John, II ;

Harker, Graydon ;

Masuda, Norikazu ;

Petrakova, Katarina ;

Guerrero Zotano, Angel ;

Iannotti, Nicholas ;

Rodriguez, Gladys ;

Tassone, Pierfrancesco ;

Wong, Alvin ;

Bryce, Richard ;

Ye, Yining ;

Yao, Bin ;

Martin, Miguel .

LANCET ONCOLOGY, 2016, 17 (03) :367-377

[8] Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis [J].

Cortazar, Patricia ;

Zhang, Lijun ;

Untch, Michael ;

Mehta, Keyur ;

Costantino, Joseph P. ;

Wolmark, Norman ;

Bonnefoi, Herve ;

Cameron, David ;

Gianni, Luca ;

Valagussa, Pinuccia ;

Swain, Sandra M. ;

Prowell, Tatiana ;

Loibl, Sibylle ;

Wickerham, D. Lawrence ;

Bogaerts, Jan ;

Baselga, Jose ;

Perou, Charles ;

Blumenthal, Gideon ;

Blohmer, Jens ;

Mamounas, Eleftherios P. ;

Bergh, Jonas ;

Semiglazov, Vladimir ;

Justice, Robert ;

Eidtmann, Holger ;

Paik, Soonmyung ;

Piccart, Martine ;

Sridhara, Rajeshwari ;

Fasching, Peter A. ;

Slaets, Leen ;

Tang, Shenghui ;

Gerber, Bernd ;

Geyer, Charles E., Jr. ;

Pazdur, Richard ;

Ditsch, Nina ;

Rastogi, Priya ;

Eiermann, Wolfgang ;

von Minckwitz, Gunter .

LANCET, 2014, 384 (9938) :164-172

[9]

Ejlertsen B, 2018, CANCER RES, V78

[10] TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases [J].

Freedman, Rachel A. ;

Gelman, Rebecca S. ;

Anders, Carey K. ;

Melisko, Michelle E. ;

Parsons, Heather A. ;

Cropp, Anne M. ;

Silvestri, Kelly ;

Cotter, Christine M. ;

Componeschi, Kathryn P. ;

Marte, Juan M. ;

Connolly, Roisin M. ;

Moy, Beverly ;

Van Poznak, Catherine H. ;

Blackwell, Kimberly L. ;

Puhalla, Shannon L. ;

Jankowitz, Rachel C. ;

Smith, Karen L. ;

Ibrahim, Nuhad ;

Moynihan, Timothy J. ;

O'Sullivan, Ciara C. ;

Nangia, Julie ;

Niravath, Polly ;

Tung, Nadine ;

Pohlmann, Paula R. ;

Burns, Robyn ;

Rimawi, Mothaffar F. ;

Krop, Ian E. ;

Wolff, Antonio C. ;

Winer, Eric P. ;

Lin, Nancy U. .

JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (13) :1081-+

← 1 2 3 4 →