Neratinib, an oral, irreversible pan-HER tyrosine kinase inhibitor, is approved in Europe for extended adjuvant treatment in adult patients with HER2-positive/hormone receptor (HR)-positive early breast cancer who have completed adjuvant trastuzumab-based therapy within the previous year. The phase 3 ExteNET trial demonstrated that neratinib significantly improved 2-year invasive disease-free survival (IDFS) compared with placebo (Δ4.5%; hazard ratio, 0.49; 95% confidence interval [CI], 0.30-0.78), with an IDFS rate of 95.3% observed for neratinib-treated patients. This article summarizes the real-world adherence, safety, and effectiveness from the ELEANOR study that was conducted in Germany, Austria, and Switzerland.

ELEANOR (NCT04388384) was a prospective, longitudinal, observational study enrolling female patients with HER2-positive/HR-positive early breast cancer who received neratinib as extended adjuvant therapy according to the approved label. Patients who had completed adjuvant trastuzumab-based therapy within the prior year were eligible for inclusion. The primary objective was to assess adherence to neratinib, defined as intake on ≥75% of treatment days as planned by the physician. Data were collected from July 2020 to May 2023 across 66 clinical sites.

A total of 298 evaluable patients were enrolled in the study, with 285 included in the main analysis set (MAS), 287 in the safety set (SAF), 279 in the compliance set, and 82 in the patient-reported outcomes set (PROS). The median age at inclusion was 52 years. Prior to neratinib, 38.9% of patients received adjuvant/post-neoadjuvant trastuzumab monotherapy, 32.6% received adjuvant/post-neoadjuvant trastuzumab plus pertuzumab, and 23.5% received post-neoadjuvant ado-trastuzumab emtansine in the MAS. Median neratinib treatment duration in the SAF was 11.9 months (interquartile range [IQR], 4.9-12.0 months). Neratinib starting dose was <240 mg/day in 44.3% of patients in the SAF; planned dose escalation was the reason for a reduced starting dose in 89.8% of them, and 80.3% of them had a documented dose increase in the SAF. The median absolute dose intensity was 230.7 mg/day (IQR, 181.5-240.0 mg/day) in the SAF. A total of 86.4% of patients received diarrhea prophylaxis in the SAF. Adherence rate to neratinib treatment was 96.8%. At an estimated median observation time of 29.1 months (IQR, 20.5-38.3), 3.9% of patients in the MAS experienced a relapse. Relapse occurred while on neratinib treatment in 3 patients, while for 8 patients, relapse occurred in the follow-up period. The 24-month disease-free survival rate was 96.6 (95% CI, 93.5-98.2) in the MAS. At the beginning of neratinib treatment, patients’ self-rated overall health was 74.9 ± 1.8 points (mean ± SEM) on the EQ-5D-5L Visual Analogue Scale (range, 1-100) in the PROS. In the PROS, patients’ self-rated overall health slightly decreased within the first 3 months of neratinib treatment (maximum change from baseline, –6.2 ± 2.2 points [mean ± SEM]), and recovered thereafter. Treatment-emergent adverse events (TEAEs) in the SAF were consistent with the known safety profile of neratinib, with grade ≥3 diarrhea observed in 20.6% of patients. Serious TEAEs occurred in 7.3% of patients and TEAEs leading to discontinuation of neratinib occurred in 25.8% of patients.

The ELEANOR study provides valuable real-world evidence supporting the clinical benefit and manageable safety profile of extended adjuvant neratinib in patients with HER2-positive/HR-positive early breast cancer who completed adjuvant trastuzumab-based therapy within the prior year. High adherence rates and outcomes consistent with phase 3 data reinforce the role of neratinib as an effective option for reducing recurrence risk in this patient population. These findings highlight the importance of real-world studies in validating clinical trial results and optimizing patient care in routine practice.

Source: Lüftner DI, Bartsch R, Breitenstein U. Extended adjuvant neratinib in HER2+/HR+ early breast cancer in clinical routine: final results from the multi-national, prospective, observational study ELEANOR. Presented at: ESMO Congress 2025. October 20, 2025; Berlin, Germany. Abstract 299P.