M. Gnant (Vienna, Austria)

Medical University of Vienna

Author Of 2 Presentations

 On-Demand ePoster Display

24P - Consensus on the utility of breast cancer multigene signatures in routine clinical practice among European Breast Cancer clinicians - The PROCURE project.

Abstract

Background

Several genomic assays are available to profile early breast cancer (BC) that, according to current evidence, can provide reliable information including the risk of recurrence. However, little is known regarding their current use and the perception of utility across Europe. The PROCURE project aims to develop a consensus on the utility of breast cancer multigene signatures (BCMS) in treatment decision making for different eBC patient profiles based on the opinion of a panel of experts.

Methods

A Scientific Committee of 8 experts in BC from 8 European countries developed a Delphi questionnaire to be administered in two-waves to experienced clinicians across Europe, selected based on their experience in BC. The questionnaire includes 5 sections in order to characterize the participants and their expertise in BCMS, to understand the current clinical practice in eBC and the use of BCMS, to recall the participant’s opinion on the utility of the BCMS in eBC according to the patient profiles, to define recommendations on the use of BCMS in clinical practice and finally, to identify unmet needs and future applications of BCMS. 180 participants, including medical oncologists, surgeons, pathologists and gynaecologists, are expected to answer anonymously the online Delphi questionnaire. 70% agreement will be used to determine consensus on a topic.

Results

At the end of January 2021, 146 participants from 11 European countries (Austria, Denmark, France, Germany, Italy, Norway, Portugal, Spain, Sweden, Switzerland and the UK) registered to participate. 61 of them had already fully completed the 1st wave Delphi questionnaire. Results from the 1st wave will be presented to engage larger discussion with congress participants.

Conclusions

The PROCURE Project will provide useful information regarding how BCMS are currently used in clinical practice across Europe and will help to measure the utility attributed to the different BCMS by BC experts for their daily clinical practice, to establish recommendations on the use of BCMS to make treatment decision in different eBC patient profiles and to define current unmet needs and future applications of BCMS according to experts point of view.

Editorial acknowledgement

Adelphi Targis SL.

Legal entity responsible for the study

Veracyte Inc.

Funding

Veracyte Inc.

Disclosure

G. Curigliano: Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Veracyte; Advisory/Consultancy: Genomic health; Advisory/Consultancy: Ellipsis. F. Cardoso: Honoraria (self): Amgen; Honoraria (self): Astellas/Medivation; Honoraria (self): AstraZeneca; Honoraria (self): Celgene; Honoraria (self): Daiichi Sankyo; Honoraria (self): GE Oncology; Honoraria (self): Genentech; Honoraria (self): GlaxoSmithKline; Honoraria (self): Macrogenics; Honoraria (self): Medscape; Honoraria (self): Merck-Sharp; Honoraria (self): Merus BV; Honoraria (self): Mylan; Honoraria (self): Mundipharma; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self): priME Oncology; Honoraria (self): Roche; Honoraria (self): Samsung Bioepis; Honoraria (self): Eisai. M.I. Gnant: Honoraria (self): Veracyte; Honoraria (self): Amgen; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self): Daiichi Sankyo; Honoraria (self): Tolmar; Honoraria (self): LifeBrain. A-V. Lænkholm: Honoraria (self): Veracyte. F. Penault-Llorca: Honoraria (self), Research grant/Funding (self): Veracyte; Honoraria (self), Research grant/Funding (self): Exact science former Genomic Health; Honoraria (self): Agendia; Honoraria (self), Research grant/Funding (self): Myriad. A. Prat: Honoraria (self): Veracyte; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Amgen; Advisory/Consultancy: BMS; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Puma Biotechnology; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: AbbVie; Honoraria (institution): NanoString technologies; Research grant/Funding (institution): Incyte; Honoraria (self): Oncolytics; Honoraria (self), Research grant/Funding (self): Novartis; Advisory/Consultancy: Peptomyc; Honoraria (self), Advisory/Consultancy: Guardian health; Honoraria (self), Shareholder/Stockholder/Stock options: Reveal genomics; Advisory/Consultancy: AstraZeneca; Research grant/Funding (self): Incyte. All other authors have declared no conflicts of interest.

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45P - Long-term Efficacy of Neratinib in HER2-Positive Early-Stage Breast Cancer: Overall Survival and Central Nervous System Outcomes from the Phase 3 ExteNET Trial

Abstract

Background

Neratinib (Nerlynx®) is an irreversible pan-HER inhibitor that significantly improves invasive disease-free survival (iDFS) vs placebo as extended adjuvant therapy in HER2-positive (HER2+) early-stage breast cancer (eBC) after trastuzumab-based therapy. The phase III ExteNET trial (NCT00878709) showed an absolute iDFS benefit of 2.5% and distant disease-free survival benefit of 1.7% with neratinib after 5 years’ follow-up. The brain is a common first site of metastasis after HER2-directed adjuvant therapy for eBC. To date, no HER2-directed therapies have prevented central nervous system (CNS) metastases in this setting.

Methods

Women with HER2+ eBC who had completed adjuvant therapy (± neoadjuvant therapy) with trastuzumab + chemotherapy were randomized to oral neratinib 240 mg/d or placebo for 1y. OS was analyzed after 248 events (powered for the ITT population). CNS outcomes: cumulative incidence of CNS recurrences (time from randomization to CNS recurrence as first distant recurrence); CNS disease-free survival (CNS-DFS, time from randomization to any CNS recurrence or death from any cause). Cut-off dates: 5y (Mar 2017); OS (Jul 2019).

Results

2840 patients were randomized (1420 per group). After a median follow-up of 8.1y, 8y OS rates were 90.1% (95% CI 88.3‒91.6) for neratinib and 90.2% (95% CI 88.4‒91.7) for placebo (absolute difference –0.1%; stratified HR=0.95; 95% CI 0.75‒1.21; p=0.6914). At 5y, cumulative incidence of CNS recurrences was 1.3% (95% CI 0.8–2.1) with neratinib and 1.8% (95% CI 1.2–2.7) with placebo, and CNS-DFS rates were 97.5% (95% CI 96.4–98.3) and 96.4% (95% CI 95.2–97.4), respectively (HR=0.73; 95% CI 0.45–1.17). No new safety signals were reported.

Conclusions

There were fewer deaths with neratinib than placebo in ExteNET, but the results did not reach statistical significance. Long-term CNS outcomes at 5y were also improved with neratinib. Neratinib is the first HER2-directed agent to show a trend towards improved CNS outcomes in HER2+ eBC, providing further support for current NCCN guidelines that recommend neratinib-based therapy for brain metastases from HER2-positive breast cancer.

Clinical trial identification

NCT00878709.

Editorial acknowledgement

Lee Miller, Miller Medical Communications Ltd.

Legal entity responsible for the study

Puma Biotechnology Inc.

Funding

Puma Biotechnology Inc.

Disclosure

B. Moy, I. Gore: Research grant/Funding (institution): Puma Biotechnology Inc. R.P. Bryce, F. Xu, A. Wong: Shareholder/Stockholder/Stock options, Full/Part-time employment: Puma Biotechnology Inc. F.A. Holmes: Travel/Accommodation/Expenses: Puma Biotechnology Inc. All other authors have declared no conflicts of interest.

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