Marija Balic (Graz, Austria)

Medical University of Graz

Author Of 2 Presentations

Proffered Paper session 2 (ID 8)

58O - Safety interim analysis (SIA) of the phase III postneoadjuvant SASCIA study evaluating sacituzumab govitecan (SG) in patients with primary HER2-negative breast cancer (BC) at high relapse risk after neoadjuvant treatment. (ID 279)

Abstract

Background

SASCIA (NCT04595565) is an ongoing phase III study randomising patients (pts) with HER2- BC and residual disease after neoadjuvant chemotherapy (NACT) or hormone receptor (HR)+ with a CPS+EG score ≥3 or 2 and ypN+ after NACT to SG or treatment of physicianś choice (TPC, capecitabine, platinum, observation). We present the results of the pre-planned SIA.

Methods

The analysis was performed after the first 50 randomized pts had completed 4 therapy cycles. Pts were included if they received ≥2 cycles, were observed ≥6 wks or discontinued earlier. Objectives were to assess adverse events (AEs) grade (G) 1-4, G3-4 and compliance (dose reductions, delays, discontinuation) between arms.

Results

At the time of the analysis, 142 pts were randomized, 88 were included in the SIA. 45 pts received SG, 32 capecitabine, 11 were observed. Median age was 46 (24-71) in SG vs 51 (32-74) yrs in TPC arm, median BMI (25.8 (20.0-42.6) vs 23.8 (18.2-35.4) kg/m2), more pts in SG arm had a Ki67>20% (N=29, 64.4% vs N=21, 48.8%); 30 (66.7%) vs 29 (67.4%) were HR-, 15 (33.3%) vs 14 (32.6%) HR+. All pts had AEs G1-4 in SG arm vs 37 (86.0%) in TPC arm, and 30 (66.7%) vs 9 (20.9%) G3-4 (Table), no death occurred. 6 (13.6%) pts under SG vs 3 (9.4%) under capecitabine discontinued therapy prematurely; 30 (66.7%) vs 13 (43.2%) had ≥1 dose delay, due to hematological (N=21, 46.7% vs N=3, 10.0%) and non-hematological AEs (N=3, 6.7% vs N=7, 23.3%); 12 (26.7%) vs 9 (28.1%) had ≥1 dose reduction (hematological N=6, 13.3% vs N=1, 3.1%; non-hematological N=5, 11.1% vs N=6, 18.8%).

Statistically significant different AEs between arms

G1-4 N % G3-4 N %
SG TPC* p-value SG TPC* p-value#
Any hematological 44 97.8 29 72.5 0.001 25 55.6 0 0 <0.001
Anaemia 36 80.0 15 39.5 0.011 1 2.2 0 0 <0.001
Leukopenia 44 97.8 24 63.2 <0.001 13 28.9 0 0 1.000
Neutropenia 37 82.2 12 31.6 <0.001 19 42.2 0 0 <0.001
Any non-hematological 45 100 36 83.7 0.005 15 33.3 9 20.9 0.235
Nausea 27 60.0 11 27.5 0.004 2 4.4 0 0 0.496
Vomiting 11 24.4 1 2.5 0.004 0 0 0 0 na
Constipation 15 33.3 4 10.0 0.017 0 0 0 0 na
Diarrhea 21 46.7 9 22.5 0.024 2 4.4 1 2.5 1.000
Alopecia 31 68.9 5 12.5 <0.001 0 0 0 0 na
Palmar plantar erythrodysaesthesia 2 4.4 13 32.5 0.001 0 0 3 7.5 0.100

*Observation: 3 missings in any hematological AEs#Fisher's exact test SG vs TPC

Conclusions

SG showed a higher rate of AEs compared to TPC, which includes observation only. AEs, especially G3-4 AEs rate were in line with the known safety profile of SG and led to more dose delays. AEs due to SG therapy was well manageable using the recommended supportive measures. The study continues as planned.

Clinical trial identification

NCT04595565.

Legal entity responsible for the study

German Breast Group.

Funding

The trial is financially supported by Gilead Sciences, Inc.

Disclosure

F. Marmé: Financial Interests, Personal and Institutional, Research Grant, Grant, Personal fees: Gilead/Immunomedics; Financial Interests, Personal, Other, Personal fees: Roche, AstraZeneca, Pfizer, Tesaro, Novartis, Amgen, PharmaMar, Genomic Health, CureVac, Eisai, BMS, Clovis, Janssen-Cilag, GSK, MSD, Seagen, Myriad, Pierre Fabre. C. Hanusch: Financial Interests, Personal, Other, Personal Fees: Roche, Novartis, Lilly, AstraZeneca. T. Link: Financial Interests, Personal, Other: Pfizer, Roche, Tesaro, Amgen, Novartis, Lilly, Myriad, Eisai, Gilead; Non-Financial Interests, Personal, Other: MSD, Clovis, GSK; Non-Financial Interests, Institutional, Other: BMS, Daiichi Sankyo. C. Denkert: Financial Interests, Personal, Ownership Interest, Stock and Other Ownership Interests: Sividon Diagnostics; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca Merck, Lilly; Financial Interests, Personal and Institutional, Advisory Role, Consulting or Advisory Role, Research Funding: Roche; Financial Interests, Institutional, Research Grant, Research Funding: Myriad Genetics; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: VMScope Digital Pathology Software, WO2015114146A1, WO2010076322A1, WO2020109570A1. P.A. Fasching: Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Novartis, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Seagen, Roche, Gilead; Financial Interests, Institutional, Research Grant, Grant: BioNTech, Cepheid; Financial Interests, Personal and Institutional, Advisory Board, Advisory Board, Invited Speaker, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory Board: Pierre Fabre, Hexal, Agendia, Sanofi Aventis. C. Jackisch: Financial Interests, Personal, Other: Roche, AstraZeneca, Pfizer, Lilly, Novartis, Exact Sciences; Financial Interests, Institutional, Other: Seagen. P. Aftimos: Financial Interests, Personal, Other: Boehringer Ingelheim, Macrogenics, Amcure, Synthon, Servier, G1 Therapeutics, Novartis, Radius, Deloitte, Menarini, Gilead; Non-Financial Interests, Personal, Other, Travel Grant: Roche; Non-Financial Interests, Institutional, Other, Travel Grant: Amgen, MSD, Pfizer. J. Huober: Financial Interests, Personal, Other: Gilead, Seagen, Roche, MSD, AbbVie, Eisai; Financial Interests, Personal and Institutional, Research Grant, Grant: Lilly; Financial Interests, Personal and Institutional, Research Grant, Grant, Travel, Other: Novartis; Financial Interests, Personal, Other, Travel, Other: Pfizer, Daiichi; Financial Interests, Institutional, Research Grant, Grant: Hexal; Financial Interests, Institutional, Research Grant, Grant, Travel: BMS. M. Untch: Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Amgen GmbH, AstraZeneca, Celgene GmbH, Daiichi Sankyo, Eisai, Lilly Int., MSD Merck, Myriad Genetics, Pfizer GmbH, Roche Pharma AG, Sanofi Aventis Deutschland GmbH, Novartis, Clovis Oncology; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: BMS, Lilly Deutschland, Pierre Fabre, Seattle Genetics, Seagen, GSK, Gilead. M. Balic: Financial Interests, Institutional, Research Grant, Grants: ABCSG; Financial Interests, Institutional, Research Grant, Grant, Consulting fees, Payment or honoraria for lectures, Support for attending meetings, travel, Data safety board or advisory board: AstraZeneca, Eli Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche; Financial Interests, Institutional, Research Grant, Grant, Consulting fees, Payment or honoraria for lectures, Data safety board or advisory board: Daiichi Sankyo, Seagen; Financial Interests, Institutional, Research Grant, Grant, Consulting fees, Payment or honoraria for lectures: Samsung. M. Reinisch: Financial Interests, Personal, Other: AstraZeneca, Novartis, Roche, Pfizer, Somatex, Daiichi Sankyo, Lilly MSD. J. Blohmer: Financial Interests, Personal, Advisory Role, Consulting or Advisory Role, Honoraria: Amgen, AstraZeneca, Novartis; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role, Travel, Accommodations, Expenses, Honoraria: Pfizer, Roche; Financial Interests, Personal, Other, Honoraria: MSD Oncology, Lilly, Gilead Sciences, Eisai Germany, Seattle Genetics, Daiichi Sankyo/AstraZeneca, Exact Sciences, Molecular Health. S. Loibl: Financial Interests, Institutional, Research Grant, Grant, Other: AbbVie, AstraZeneca, Celgene; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Amgen, Bayer, BMS; Non-Financial Interests, Institutional, Advisory Board, Honorarium for Ad Board & Lecture, Medical Writing: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Eirgenix, GSK, Lilly, Merck; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Immunomedics/Gilead; Non-Financial Interests, Institutional, Advisory Board, honorarium for Ad Board & Lectures, Medical Writing, Grant, Other: Novartis, Pfizer, Roche; Financial Interests, Institutional, Advisory Board, Honorarium for Ad Board & Lecture, Other: Pierre Fabre, prIME/Medscape; Non-Financial Interests, Institutional, Advisory Board, Honorarium for Ad Board, Medical Writing, Other: Puma, Seagen; Financial Interests, Institutional, Advisory Board, honorarium for Lecture, Other: Samsung; Other, Institutional, Other, Patent Pending: EP14153692.0, EP21152186.9; Other, Institutional, Other, Patent Issued: EP15702464.7; Other, Institutional, Other, Patent Pending, GeparNuevo: EP19808852.8; Other, Institutional, Royalties, Patent Issued, Royalties: Digital Ki67 Evaluator. All other authors have declared no conflicts of interest.

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Poster Display session (ID 9)

75P - Interim analysis (n=150) of the multi-national, prospective, non-interventional ELEANOR study observing real-life extended adjuvant treatment with neratinib in patients with HER2+ / HR+ early breast cancer (eBC) (ID 90)

Abstract

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.

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