Related Experiment Video
Updated: Nov 30, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the
Arlene Chan1, Beverly Moy2, Janine Mansi3
1Breast Clinical Trials Unit, Breast Cancer Research Centre-WA & Curtin University, Perth, Australia.
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.
Insights
Neratinib significantly improved invasive disease-free survival (iDFS) in patients with HER2-positive, hormone receptor-positive early-stage breast cancer within one year of trastuzumab therapy. This suggests a potential long-term benefit for neratinib in this specific patient group.
Area of Science:
- Oncology
- Pharmacology
Background:
- The ExteNET trial investigated neratinib's efficacy in early-stage breast cancer (eBC).
- Neratinib is a pan-HER tyrosine kinase inhibitor targeting HER2-positive (HER2+) cancers.
- Hormone receptor-positive (HR+) HER2+ eBC patients often have complex treatment needs.
Purpose of the Study:
- To evaluate the efficacy of neratinib versus placebo in HER2+/HR+ eBC patients.
- To assess the impact of treatment timing relative to trastuzumab therapy on neratinib's effectiveness.
- To analyze invasive disease-free survival (iDFS) and overall survival (OS) in distinct patient subgroups.
Main Methods:
- A multicenter, randomized, double-blind, phase III trial involving 2840 patients with HER2+ eBC.
- Patients received neoadjuvant/adjuvant trastuzumab-based therapy before randomization to 1-year oral neratinib or placebo.
- Stratification by HR status and analysis of subgroups based on treatment initiation time post-trastuzumab (≤1 year vs. >1 year).
Main Results:
- Neratinib significantly improved 5-year iDFS by 5.1% in the HR+/≤1-year group (HR, 0.58).
- A trend towards improved 8-year OS was observed in the HR+/≤1-year group (absolute benefit, 2.1%).
- Patients with residual disease after neoadjuvant therapy showed substantial iDFS and OS benefits with neratinib.
Conclusions:
- Neratinib significantly enhances iDFS in HER2+/HR+ eBC patients treated within one year of trastuzumab.
- The drug demonstrates a positive trend in overall survival and benefits patients with residual disease.
- Neratinib offers a potential long-term therapeutic option for specific HER2+ early-stage breast cancer populations.
More Related Videos
11:12Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
09:32Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
Published on: October 17, 2025
