Background

Neratinib is registered in Europe as extended adjuvant treatment for adult patients with Human Epidermal Growth Factor Receptor 2-positive (HER2+) and Hormone receptor-positive (HR+) eBC within one year after completed adjuvant trastuzumab-based therapy (“EMA-/Swiss-label” population). In the ExteNET trial, extended adjuvant neratinib improved the absolute 5-year invasive disease-free survival rate by 5.1% vs. placebo in this population (90.8% vs. 85.7%; HR 0.58 [95% CI 0.41-0.82]). More pronounced benefit was observed in patients with non-pCR after neoadjuvant trastuzumab-based therapy and/or in patients who completed one year of neratinib (descriptive post-hoc analyses). In the absence of primary prophylaxis, grade 3 diarrhea occurred in 39% of patients in the ExteNET trial. ELEANOR is the first study to investigate real-world use of neratinib and its management in eBC patients in Germany, Austria and Switzerland.

Methods

300 patients with HER2+/HR+ eBC will be enrolled in accordance with the specifications of the local Summary of Product Characteristics. Primary objective is the proportion of patients adherent to neratinib treatment (i.e., neratinib intake for ≥75% of treatment days). Secondary objectives include analysis of prior trastuzumab-based therapies (including pertuzumab and T-DM1), neratinib dosing and management, relapses, safety / tolerability, and health-related quality of life (using the CANKADO eHealth application).

Results

Between July 2020 and Feb 2022, 206 patients were enrolled at 59 sites; patient enrollment is ongoing. We will present results from the interim analysis on the first 150 enrolled patients who have been observed for at least 3 months (data cut Nov 2021, analyses ongoing). Baseline demographics and tumor characteristics, prior trastuzumab-based treatments, and neratinib safety and tolerability will be reported.

Conclusions

ELEANOR will help to characterize adherence to neratinib and use of extended adjuvant HER2-targeted therapy in the current treatment landscape focusing on neratinib management after different prior therapies.

Editorial acknowledgement

Editorial assistance was provided by Anna Resch, Pierre Fabre Pharma GmbH, Freiburg, Germany.

Legal entity responsible for the study

Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland).

Funding

Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland).

Disclosure

N. Harbeck: Financial Interests, Personal, Other: Amgen, AstraZeneca, Daiichi Sankyo, Exact Sciences, Eli Lilly, Gilead, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Seagen, WSG; Financial Interests, Institutional, Other: clinical trials. D. Wrobel: Financial Interests, Personal, Other: Roche, Novartis. M. Zaiss: Financial Interests, Personal, Other: Celgene, AstraZeneca, RG, AKS, Vifor, Pfizer, Janssen, Novartis, AbbVie; Financial Interests, Personal and Institutional, Other: Roche, Eli Lilly; Financial Interests, Institutional, Other: GBG. R. Bartsch: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Daiichi; Financial Interests, Institutional, Invited Speaker, Drug support for investigator initiated trial: MSD. U. Breitenstein: Financial Interests, Institutional, Other: Novartis, Roche, AstraZeneca, Eli Lilly, Pierre Fabre, Pfizer, SAKK; Non-Financial Interests, Personal, Other: SGMO, SGS, SAKK. M. Schwitter: Financial Interests, Personal and Institutional, Other: Pierre Fabre. M. Balic: Financial Interests, Personal, Other: Amgen, Pierre Fabre, Daiichi Sankyo, Bayer, Samsung, Seagen; Financial Interests, Personal and Institutional, Other: Novartis, Eli Lilly, Pfizer, Celgene, AstraZeneca, MSD, Roche; Financial Interests, Institutional, Other: ABCSG, IBCSG, BIG. C. Jackisch: Financial Interests, Personal, Other: Roche, AstraZeneca, Eisai, Pfizer, Eli Lilly, Novartis, Exact Sciences; Non-Financial Interests, Personal, Other: Roche. V. Müller: Financial Interests, Personal, Other: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead; Financial Interests, Institutional, Other: Novartis, Roche, Seattle Genetics, Genentech. G. Rinnerthaler: Financial Interests, Personal and Institutional, Other: Roche, Pierre Fabre; Financial Interests, Personal, Other: AstraZeneca, Novartis, BMS, Roche, Pfizer, Eli Lilly, MSD, Daiichi Sankyo. M. Schmidt: Financial Interests, Personal, Other: Amgen, Seagen; Financial Interests, Personal and Institutional, Other: Pierre Fabre, Roche, Pfizer, Novartis, AstraZeneca, Eisai, Pantarhei, BioNTech; Financial Interests, Institutional, Other: Genentech; Non-Financial Interests, Personal, Other: Roche, Pfizer, Pantarhei, BioNTech; Non-Financial Interests, Personal, Other, Issued patent EP: 2951317, Issued patent EP: 2390370: Other. K. Zaman: Financial Interests, Personal and Institutional, Other: Roche; Financial Interests, Institutional, Other: Eli Lilly, Novartis, MSD Oncology, Mylan, Daiichi Sankyo, Pierre Fabre, Genentech. T. Schinköthe: Financial Interests, Personal, Full or part-time Employment: CANKADO Service GmbH; Financial Interests, Personal, Ownership Interest: CANKADO Service GmbH. D. Lüftner: Financial Interests, Institutional, Other: Novartis; Financial Interests, Personal, Other: Amgen, Pfizer, GSK, Loreal, Teva, Gilead, Sanofi Aventis, Daiichi Sankyo, Samsung, AstraZeneca, Novartis. All other authors have declared no conflicts of interest.

Background

Up to 30% of metastatic breast cancer (BC) patients (pts) develop brain metastases (BM). Prognosis of pts with BM is poor and long-term survival is rare. Identification of factors associated with long-term survival is important for improving treatment modalities.

Methods

A total of 2889 out of 3234 pts of the BMBC registry were available for this analysis. Long-term survival was defined as overall survival (OS) in the upper third of the survival curve resulting in a cut-off of 15 months. 887 patients were categorized as long-term survivors.

Results

Long-term survivors compared to other pts were younger at BC and BM diagnosis (median 48 vs 54 years and 53 vs 59 years), had more often HER2+ tumors (59.1% vs 36.3%), less frequently luminal-like (29.1% vs 35.7%) or TNBC (11.9% vs 28.1%), showed better ECOG at time of BM diagnosis (ECOG 0-1 76.9% vs 51.0%), higher pCR rate (21.6% vs 13.7%) and lower number of BM (n=1 BM 40.9% vs 25.4%; n=2-3 BM 26.5% vs 26.7%; n≥4 BM 32.6% vs 47.9%) (p<0.001). Long-term survivors had less leptomeningeal metastases (10.4% vs 17.5%) and extracranial metastases (ECM, 73.6% vs 82.5%), and more often asymptomatic BM at time of BM diagnosis (26.5% vs 20.1, p<0.001). Median OS in long-term survivors was 30.9 months (95% CI 28.8-32.6) overall, 33.9 (95% CI 31.5-37.9) in HER2+, 26.9 (95% CI 25.0-30.9) in luminal-like and 26.5 (95% CI 22.7-31.2) in TNBC pts. Factors significantly associated with a categorization of long-term survivors are presented in the table below. Table: 170P

Multivariate logistic regression in long-term vs short-term survivors

Conclusions

Our analysis identified factors associated with long-term survival of BC pts with BM and characterized clinical features of this patient cohort. Pts with better ECOG status, younger age, lower number of BM, less extended visceral metastases are more likely to show a long-term survival and therefore are more eligible for extended local and systemic treatment.

Legal entity responsible for the study

GBG Forschung.

Funding

Partial Funding Daiichi Sankyo Europe.

Disclosure

M. Schmidt: Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Other: Pantarhei; Financial Interests, Personal, Other: BioNTech; Financial Interests, Personal, Other: Genentech; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: MSD. J. Puppe: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Synlab; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Invited Speaker: Novartis. K. Lübbe: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Eisei; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche. M. Thill: Financial Interests, Personal, Advisory Board: Sysmex; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: RTI Surgical; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: pfm Medical; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Onkowissen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Neodynamics; Financial Interests, Personal, Advisory Board: Norgine; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Gilead Science; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: ClearCut; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Biom‘Up; Financial Interests, Personal, Advisory Board: Becton/Dickinson; Financial Interests, Personal, Advisory Board: Aurikamed; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Funding: Endomag; Financial Interests, Personal, Funding: Exact Sciences; Financial Interests, Personal, Invited Speaker: Viatris; Financial Interests, Personal, Invited Speaker: Vifor; Financial Interests, Personal, Invited Speaker: Sysmex; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Invited Speaker: RTI Surgical; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: pfm Medical; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Omniamed; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Medtronic; Financial Interests, Personal, Invited Speaker: MCI; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Jörg Eickeler; Financial Interests, Personal, Invited Speaker: I-Med-Institute; Financial Interests, Personal, Invited Speaker: Hexal; Financial Interests, Personal, Invited Speaker: Gilead Science; Financial Interests, Personal, Invited Speaker: Exact Sciences; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Connect Medica; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Art Tempi; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other: Clear Cut. C. Denkert: Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Molecular Health; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Ownership Interest, Cofounder and shareholder of Sividon Diagnostics until 2016: Sividon Diagnostic; Financial Interests, Personal, Invited Speaker: VmScope digital pathology software; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Research Grant: Myriad. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: AbbVie; Financial Interests, Institutional, Advisory Board, Member: Amgen; Financial Interests, Institutional, Advisory Board, Member: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board, Member: Bayer; Financial Interests, Institutional, Advisory Board, Member: BMS; Financial Interests, Institutional, Advisory Board, Member: Celgene; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Institutional, Advisory Board: DSI; Financial Interests, Institutional, Invited Speaker: DSI; Financial Interests, Institutional, Advisory Board, Member: EirGenix; Financial Interests, Institutional, Advisory Board, Member: GSK; Financial Interests, Institutional, Invited Speaker: Ipsen; Financial Interests, Institutional, Advisory Board, Member: Lilly; Financial Interests, Institutional, Advisory Board: Merck KG; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board, Member: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board, Member: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: prIME/Medscape; Financial Interests, Institutional, Advisory Board, Member: prIME/Medscape; Financial Interests, Institutional, Advisory Board, Member: Puma; Financial Interests, Institutional, Advisory Board, Member: Roche; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Samsung; Financial Interests, Institutional, Advisory Board, Member: Seagen; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Invited Speaker, Ki67: VM Scope GmbH; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: AbbVie; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics; Financial Interests, Personal, Other, SC HERCLIMB: Seagen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Funding: Cepheid; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Invited Speaker, Executive Board: BIG; Non-Financial Interests, Other, Medical Writing: Amgen; Non-Financial Interests, Other, Medical Writing: AstraZeneca; Non-Financial Interests, Other, Medical Writing: BMS; Non-Financial Interests, Other, Medical Writing: Celgene; Non-Financial Interests, Other, Medical Writing: Daiichi Sankyo; Non-Financial Interests, Other, Medical Writing: Novartis; Non-Financial Interests, Other, Medical Writing: Pfizer; Non-Financial Interests, Other, Medical Writing: Roche; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member, Chair ESMO Breast; SC: ESMO; Other, EP18209672.7No financial interest, Institutional: Patent; Other, EP21152186.9No financial interest, institutional: Patent; Other, EP15702464.7No financial interest, institutional: Patent. V. Müller: Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Invited Speaker: Teva; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other: Gilead; Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: ClinSol; Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Hexal; Financial Interests, Personal, Other: Genomic Health; Financial Interests, Institutional, Research Grant: Seagen; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis. I. Witzel: Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca. All other authors have declared no conflicts of interest.