304P - Incidence and resolution of eribulin-induced peripheral neuropathy (IRENE) in patients with locally advanced or metastatic breast cancer

Background

Eribulin (ERI), a halichondrin-class microtubule dynamics inhibitor, is a typical chemotherapeutic regimen for patients (pts) with previously treated locally advanced or metastatic breast cancer (MBC). Results of pivotal trials showed that about one-third of pts with locally advanced or MBC treated with ERI develop peripheral neuropathy (PN), a common risk with BC chemotherapies. This postauthorization safety study assessed the incidence and severity of ERI-induced PN (EIPN) in pts with locally advanced or MBC.

Methods

IRENE is an ongoing observational, single-arm, prospective, multicenter, cohort study. Adult pts with locally advanced or MBC with progression after ≥1 prior chemotherapeutic regimen(s) for advanced disease received ERI according to routine clinical care. The planned observation period for each patient was ∼15 months; pts with EIPN (new onset or worsening of pre-existing PN) were documented until death or resolution of PN. Primary endpoints included the number of pts with EIPN, severity of EIPN, and time to treatment discontinuation (TTD) due to EIPN. Secondary endpoints included time to disease progression (TDP) and safety.

Results

This interim analysis (data cutoff: 1 July 2019) included 207 pts who received ≥1 dose of ERI; 165 of these pts discontinued ERI (most commonly due to disease progression [n=107] and adverse events [AEs; n=33]). Among the 67 (32.4%) pts who experienced EIPN, 12 pts had grade ≥3 EIPN, and 12 pts received treatment for EIPN. Six (2.9%) pts discontinued ERI due to EIPN. Median TTD due to EIPN was not estimable. Median TDP was 4.6 months (95% CI 4.0–6.5). Treatment-emergent AEs (TEAEs) occurred in 195 (94.2%) pts; 107 (51.7%) pts experienced serious TEAEs (Table).

Conclusions

Interim results of this real-world study are similar to those of pivotal ERI trials in terms of overall EIPN frequency and grade ≥3 EIPN frequency. No new safety findings emerged. Table: 304P

Pts appear in each category in which they had ≥1 event(s).^aIncludes pts who received ≥1 dose(s) of eribulin at data cutoff.^b12 pts received treatment for EIPN.^cPer the Common Terminology Criteria for Adverse Events version 4.0^dMedian time to treatment discontinuation due to EIPN was not estimable.

Clinical trial identification

NCT03027245; EnCePP number: EUPAS14118.

Editorial acknowledgement

Medical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Woodcliff Lake, NJ, USA.

Legal entity responsible for the study

Eisai GmbH.

Funding

Eisai GmbH, Frankfurt, Germany.

Disclosure

M. Schmidt: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Seagen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BioNTech; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pantarhei Bioscience; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: German Breast Group; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Palleos; Financial Interests, Institutional, Research Grant: Pantarhei Bioscience; Financial Interests, Institutional, Research Grant: Pierre-Fabre; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Personal, Member: ESMO; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: DGGG; Non-Financial Interests, Personal, Member: Senologie; Non-Financial Interests, Personal, Member: EACR; Non-Financial Interests, Personal, Member: DKK. C. Jackisch: Non-Financial Interests, Personal, Writing Engagements: Roche; Non-Financial Interests, Personal, Writing Engagements: Puma; Non-Financial Interests, Personal, Writing Engagements: AstraZeneca; Non-Financial Interests, Personal, Writing Engagements: Exact Sciences; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Institutional, Royalties: Exact Sciences; Non-Financial Interests, Personal, Principal Investigator: Roche. T. Hesse: Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Writing Engagements: Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Lilly; Financial Interests, Institutional, Principal Investigator: Novartis. O. Hoffmann: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Hexal; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Rheimser; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Seagan; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal and Institutional, Full or part-time Employment: University Hospital of Essen; Non-Financial Interests, Institutional, Principal Investigator: PrincipPhase II and III and IV studies against breast cancer e.g. WSG, GBG. B.J. Heinrich: Financial Interests, Personal, Advisory Board: Eisai. T. Park-Simon: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Tesaro; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Daichi; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Lilly; Financial Interests, Institutional, Principal Investigator: GSK; Financial Interests, Institutional, Principal Investigator: Tesaro; Financial Interests, Institutional, Principal Investigator: Seagen; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Institutional, Principal Investigator: Pierre Fabre. H. Müller-Huesmann: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Boeringer-Ingelheim; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Janssen; Non-Financial Interests, Institutional, Writing Engagements: BMS; Non-Financial Interests, Institutional, Writing Engagements: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Boeringer-Ingelheim; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Boeringer-Ingelheim; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Janssen. J. Wu: Financial Interests, Personal and Institutional, Full or part-time Employment: Eisai Inc. H. Schmitz: Financial Interests, Personal and Institutional, Full or part-time Employment: Eisai GmbH. C. Engelbrecht: Financial Interests, Personal and Institutional, Full or part-time Employment: Eisai GmbH. H. Lück: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Eisai. All other authors have declared no conflicts of interest.