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. 2024 Feb;19(1):1-9.
doi: 10.1159/000533657. Epub 2023 Oct 5.

Neratinib as Extended Adjuvant Treatment of HER2-Positive/HR-Positive Early Breast Cancer Patients in Germany, Austria, and Switzerland: Interim Results of the Prospective, Observational ELEANOR Study

Nadia Harbeck  1 , Denise Wrobel  2 , Matthias Zaiss  3 , Jürgen Terhaag  4 , Dagmar Guth  5 , Andrea Distelrath  6 , Mark-Oliver Zahn  7 , Rachel Wuerstlein  1 , Andreas Lorenz  8 , Rupert Bartsch  9 , Urs Breitenstein  10 , Michael Schwitter  11 , Marija Balic  12 , Christian Jackisch  13 , Volkmar Müller  14 , Gabriel Rinnerthaler  15 , Marcus Schmidt  16 , Khalil Zaman  17 , Timo Schinköthe  18 , Anna Resch  19 , Roberta Valenti  20 , Diana Lüftner  21
Affiliations

Neratinib as Extended Adjuvant Treatment of HER2-Positive/HR-Positive Early Breast Cancer Patients in Germany, Austria, and Switzerland: Interim Results of the Prospective, Observational ELEANOR Study

Nadia Harbeck et al. Breast Care (Basel). 2024 Feb.

Abstract

Introduction: Prognosis of patients diagnosed with HER2+ early breast cancer (eBC) has substantially improved, but distant recurrences impacting quality of life and survival still occur. One treatment option for extended adjuvant treatment of patients with HER2+/HR+ eBC is neratinib, available in Europe for patients who completed adjuvant trastuzumab-based therapy within 1 year. The ELEANOR study is investigating the real-world use of neratinib in Germany, Austria, and Switzerland. Results from an interim analysis of the first 200 patients observed for ≥3 months are reported.

Methods: The primary objective of this prospective, multicenter, observational study is to assess patient adherence to neratinib (defined as the percentage of patients taking neratinib on ≥75% prescribed days). Secondary objectives are patient characteristics and treatment outcomes.

Results: At cut-off (May 2, 2022), a total of 202 patients had been observed for ≥3 months, with neratinib treatment documented for 187 patients (median age: 53.0 years; 67.9% at increased risk of disease recurrence). In total, 151 (80.7%) patients had received prior neoadjuvant treatment; of these, 82 (54.3%) patients achieved a pathologically complete response. Neratinib was initiated at a median 3.6 months after trastuzumab-based treatment, with 36.4% starting at a dose <240 mg/day. Treatment is ongoing for 46.0% of patients, with median treatment duration of 11.2 (interquartile range 0.9-12.0) months. Diarrhea was the most common adverse event (78.6% any grade, 20.3% grade ≥3); pharmacologic prophylaxis was used in 85.6% of patients.

Conclusions: The pattern of anti-HER2 pretreatment observed reflected the current treatment for HER2+/HR+ eBC in Germany, Austria, and Switzerland. These interim results suggest that neratinib as an extended adjuvant is a feasible option after various anti-HER2 pretreatments and that its tolerability can be managed and improved with proactive diarrhea management.

Keywords: Early breast cancer; Extended adjuvant treatment; HER2-positive breast cancer; HR-positive breast cancer; Neratinib.

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Conflict of interest statement

Nadia Harbeck has received honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, and Seagen. Denise Wrobel has received honoraria from Novartis, Teva, Roche, and AstraZeneca and for lectures and travel grant from Roche, Novartis, and Pierre Fabre. Matthias Zaiss has received honoraria for lectures and/or consulting from AbbVie, AstraZeneca, BMS, Celgene, Eisai, Gilead, Hexal, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, and Vifor. Jürgen Terhaag has received funds from Aurikamed and registration fees from Lilly. Dagmar Guth has received fees for lectures and consulting from Amgen, Aristo, Astra Zeneca, Celgene, Gilead, Janssen, Lilly, Novartis, Pharma Mar, Pfizer, Ribosepharm, and Roche. Rachel Wuerstlein has acted as an advisor, consultant, or speaker for or received travel grant(s) from Agendia, Amgen, Aristo, AstraZeneca, Boehringer Ingelheim, Carl Zeiss, Celgene, Clovis Oncology, Daiichi-Sankyo, Eisai, Exact Sciences, Genomic Health, Gilead, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, Puma Biotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics, Seagen, Tesaro Bio, Teva, Veracyte, and Viatris. Rupert Bartsch has received fees from AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Grünenthal, MSD, Novartis, Pfizer, Pierre Fabre, Roche, and Seagen. Michael Schwitter has received personal fees from Pierre Fabre, Daiichi Sankyo, and Novartis. Marija Balic has received personal fees from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, MSD, Novartis, Pierre Fabre, Pfizer, Roche, and Seagen; and research funding from AstraZeneca, Daiichi Sankyo, Eli Lilly, Novartis, Pierre Fabre, Pfizer, and Seagen. Christian Jackisch has received personal fees from AstraZeneca, Daiichi Sankyo, Exact Sciences, Eisai, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Art Tempi Communications, and Med Update. Volkmar Müller has received speaker honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, onkowissen, high5 Oncology, Medscape, Gilead, and Pierre Fabre; consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Sanofi, Seagen, and Gilead; institutional research support from Novartis, Roche, Seagen, and Genentech; travel grants from Roche, Pfizer, Daiichi Sankyo, and Gilead. Gabriel Rinnerthaler has received personal fees from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, Merk, MSD, Novartis, Pfizer, Pierre Fabre, Roche, and Seagen. Marcus Schmidt has received personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche, and SeaGen; institutional research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and Seagen; and holds patents for EP 2390370 B1 and EP 2951317 B1. Khalil Zaman has received honoraria from AstraZeneca, Daiichi, Eisai, Exact Sciences, Gilead, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seagen, Viatris, and Vifor; a member of the Executive Committee of the MINDACT trial; and a member of the Swiss Group for Clinical Research against Cancer (SAKK). Timo Schinköthe is the owner of CANKADO. Diana Lüftner has received honoraria for advisory board activities and/or presentations from Amgen, AstraZeneca, Eli Lilly, Gilead, GSK, high5md, Loreal, MSD, Mundipharma, Mylan, Novartis, onkowissen, Pfizer, Pierre Fabre, Roche, Teva, and Viatris. Anna Resch and Roberta Valenti are employees of Pierre Fabre. Andrea Distelrath, Mark-Oliver Zahn, Andreas Lorenz, and Urs Breitenstein have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
Treatment duration by starting dose. CI, confidence interval.
See this image and copyright information in PMC

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