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Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial
- Source :
- 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 ', Clinical Breast Cancer, vol. 21, no. 1, pp. 80-91.e7 . https://doi.org/10.1016/j.clbc.2020.09.014, 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, Inoue, K, Ruiz-Borrego, M, Hui, R, Denduluri, N, Patt, D, Rugo, H S, Johnston, S R D, 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 ', Clinical Breast Cancer, vol. 21, no. 1, pp. 80-91.e7 . https://doi.org/10.1016/j.clbc.2020.09.014
- Publication Year :
- 2021
-
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. 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.
- Subjects :
- Adult
0301 basic medicine
Cancer Research
medicine.medical_specialty
Distant disease-free survival
Receptor, ErbB-2
Disease-free survival
medicine.medical_treatment
Population
Breast Neoplasms
Placebo
Gastroenterology
Adjuvant therapy
Disease-Free Survival
03 medical and health sciences
0302 clinical medicine
Breast cancer
Double-Blind Method
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Clinical endpoint
Humans
Overall survival
education
Neoadjuvant therapy
Neoplasm Staging
education.field_of_study
Dose-Response Relationship, Drug
business.industry
Hazard ratio
Middle Aged
medicine.disease
Treatment Outcome
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Neratinib
Quinolines
Female
business
Follow-Up Studies
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- 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 ', Clinical Breast Cancer, vol. 21, no. 1, pp. 80-91.e7 . https://doi.org/10.1016/j.clbc.2020.09.014, 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, Inoue, K, Ruiz-Borrego, M, Hui, R, Denduluri, N, Patt, D, Rugo, H S, Johnston, S R D, 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 ', Clinical Breast Cancer, vol. 21, no. 1, pp. 80-91.e7 . https://doi.org/10.1016/j.clbc.2020.09.014
- Accession number :
- edsair.doi.dedup.....9af8dc5d2e7a7a6d4d1c8bee844afef3