Abstract 247P
Background
RIBECCA was a phase 3b, multicentre, open-label study of RIB + LET in patients (pts) of any menopausal status with HR+, HER2–ABC, who were not amenable to curative treatment (tx). The study investigated RIB + LET in pt settings broader than those considered in MONALEESA (ML) studies. Data on primary endpoint, clinical benefit rate (CBR) at week 24 in cohorts A (tx naive postmenopausal pts) and B (comprising cohort B1 [tx naive pre- and perimenopausal pts] and B2 [pre-, peri- and postmenopausal pts pretreated with ≤1 prior chemotherapy and ≤2 lines of endocrine therapy]) were reported previously. Here, we report secondary efficacy and safety on prespecified cohorts B1 and B2, together with multivariate analysis on the overall study population.
Methods
Secondary endpoints of the study include CBR, and overall response rate (ORR) at week 24, progression-free survival (PFS), overall survival (OS), changes in quality of life and safety in both cohorts B1 and B2, respectively. The impact of various demographic and anamnestic factors on PFS in the overall population was evaluated using Cox regression model.
Results
In cohort B1 (n=26), confirmed CBR was (57.7% [95% CI, 36.9-76.6], ORR at week 24 was 23.1% (95% CI, 9.0-43.6) and median PFS was 16.5 months (mo; 95% CI, 3.2-not calculable). In cohort B2 (n=154), confirmed CBR was 56.5% (95% CI, 48.3-64.5), ORR at week 24 was 11.7% (95% CI, 7.1-17.8) and median PFS was 8.8 mo (95% CI, 8.1-16.3). Median OS was not reached in this study. The most common tx-emergent adverse events (grade 3/4) in cohort B1 were neutropenia (34.6%) and leucopenia (19.2%), and that in cohort B2 were neutropenia (40.8%) and neutrophil count decreased (14.0%). Baseline ECOG, histological grade, therapy situation and progesterone receptor (PR) status tended to impact PFS in multivariate analysis.
Conclusions
The data confirmed the clinical and PFS benefit of RIB + LET in both cohorts B1 and B2. Baseline ECOG, histological grade, therapy situation and PR status might impact PFS outcome. No new safety signals were observed. These results confirm findings of ML studies in broader population.
Clinical trial identification
Study number: CLEE011XDE01; NCT03096847.
Editorial acknowledgement
Dr Moon Jain.
Legal entity responsible for the study
Novartis Pharma GmbH, Germany.
Funding
Novartis Pharma GmbH, Germany.
Disclosure
T. Decker: Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Novartis; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Lilly. P.A. Fasching: Financial Interests, Personal, Advisory Board, Advisory/steering board: Novartis; Financial Interests, Institutional, Research Grant, Research Support: BioNTech; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Other, Lectures: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory board, lectures: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Institutional, Research Grant, Research Support: Cepheid; Financial Interests, Personal, Advisory Role, Advisory board, lectures: Lilly; Financial Interests, Institutional, Research Grant, Research Support: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca. A. Hartkopf: Financial Interests, Institutional, Writing Engagements, All support for the present manuscript: Novartis; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: ExactSciences; Financial Interests, Personal, Other, Consulting Fees: Novartis; Financial Interests, Personal, Other, Consulting Fees: Pfizer; Financial Interests, Personal, Other, Consulting Fees: Lilly; Financial Interests, Personal, Other, Consulting Fees: MSD; Financial Interests, Personal, Other, Consulting Fees: AstraZeneca; Financial Interests, Personal, Other, Consulting Fees: Roche; Financial Interests, Personal, Other, Consulting Fees: Seattle Genetics; Financial Interests, Personal, Other, Consulting Fees: ExactSciences; Financial Interests, Personal, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis; Financial Interests, Personal, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pfizer; Financial Interests, Personal, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Lilly; Financial Interests, Personal, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: MSD; Financial Interests, Personal, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Pfizer. B.J. Heinrich: Financial Interests, Institutional, Other, Documentation fees- for included and documented patients: Novartis. C.M. Kurbacher: Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: AstraZeneca; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: BMS; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: Eli Lilly; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: Immunomedics; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: MSD Sharp& Dohme (Merck); Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: Novartis; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: Pfizer; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: Riemser; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: Roche; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: Seattle Genetics; 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V. (BNGO). H. Tesch: Financial Interests, Personal, Other, Consulting fees: Pierre Fabre; Financial Interests, Personal, Other, Consulting fees: Pfizer Pharma; Financial Interests, Personal, Other, Consulting fees: Mundipharma; Financial Interests, Personal, Other, Consulting fees: ClinSol; Financial Interests, Personal, Other, Consulting fees: Novartis; Financial Interests, Personal, Other, Consulting fees: Lilly; Financial Interests, Personal, Other, Consulting fees: Grünenthal; Financial Interests, Personal, Other, Consulting fees: Vifor; Financial Interests, Personal, Other, Consulting fees: AstraZeneca; Financial Interests, Personal, Other, Consulting fees: Mylan; Financial Interests, Personal, Other, Consulting fees: Amgen; Financial Interests, Personal, Speaker’s Bureau, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Vifor; Financial Interests, Personal, Speaker’s Bureau, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis; 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Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Roche; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Grünenthal; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Mylan; Financial Interests, Personal, Leadership Role, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Arbeitskreis Klinische; Financial Interests, Personal, Leadership Role, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Studien e.V; Financial Interests, Personal, Leadership Role, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: ASCO; 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J. Huober: Financial Interests, Institutional, Research Grant, Research funding: Celgene; Financial Interests, Institutional, Research Grant, Research funding: Novartis; Financial Interests, Institutional, Research Grant, Research funding: Hexal; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: AbbVie; Financial Interests, Personal, Advisory Role, Consulting, advisory relationship: Lilly; Financial Interests, Personal, Advisory Role, Consulting, advisory relationship: Novartis; Financial Interests, Personal, Advisory Role, Consulting, advisory relationship: Roche; Financial Interests, Personal, Advisory Role, Consulting, advisory relationshipConsulting, advisory relationship: Pfizer; Financial Interests, Personal, Advisory Role, Consulting, advisory relationship: Hexal; Financial Interests, Personal, Advisory Role, Consulting, advisory relationship: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting, advisory relationship: MSD; Financial Interests, Personal, Advisory Role, Consulting, advisory relationship: Celgene; Financial Interests, Personal, Advisory Role, Consulting, advisory relationship: AbbVie; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Travel expenses: Pfizer; Financial Interests, Personal, Other, Travel expenses: Novartis; Financial Interests, Personal, Other, Travel expenses: Celgene; Financial Interests, Personal, Other, Travel expenses: Daiichi. S. Kümmel: Financial Interests, Personal, Other, Consulting fees: Lilly; Financial Interests, Personal, Other, Consulting fees: pfm medical; Financial Interests, Personal, Other, Consulting fees: somatex; Financial Interests, Personal, Other, Consulting fees: MSD; Financial Interests, Personal, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche; Financial Interests, Personal, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Genomic Health; Financial Interests, Personal, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis; Financial Interests, Personal, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen; Financial Interests, Personal, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Celgene; Financial Interests, Personal, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pfizer; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Daiichi Sankyo; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Lilly; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Sonoscape; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Roche; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Lilly; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: MSD; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Pfizer; Financial Interests, Personal, Member of the Board of Directors, Co-director: WSG; Financial Interests, Personal, Leadership Role, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: AGO; Financial Interests, Personal, Leadership Role, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: NOGGO e.V; Financial Interests, Personal, Leadership Role, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: AGimed. S.Y. Brucker: Financial Interests, Personal, Other, Honoraria: Storz; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: Storz; Financial Interests, Personal, Other, Travel expenses: Pfizer; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Travel expenses: Novartis; Financial Interests, Personal, Other, Travel expenses: MSD; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Advisory Board: Storz; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Astrazeneca; Financial Interests, Personal, Member of the Board of Directors, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: President DGS. W. Janni: Financial Interests, Personal, Research Grant, Grants or contracts from any entity: Novartis; Financial Interests, Personal, Other, Consulting fees: Novartis; Financial Interests, Personal, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Novartis. A. Schneeweiss: Financial Interests, Institutional, Writing Engagements, All support for the present manuscript: Roche; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: Celgene; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: Roche; Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: AbbVie; Financial Interests, Personal, Other, Consulting fees: Celgene; Financial Interests, Personal, Other, Consulting fees: Pfizer; Financial Interests, Personal, Other, Consulting fees: AstraZeneca; Financial Interests, Personal, Other, Consulting fees: Novartis; Financial Interests, Personal, Other, Consulting fees: MSD; Financial Interests, Personal, Other, Consulting fees: Tesaro; Financial Interests, Personal, Other, Consulting fees: Lilly; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Celgene; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Pfizer. M. Schuler: Financial Interests, Personal, Other, Consultant compensated: AstraZeneca; Financial Interests, Personal, Other, Consultant compensated: Boehringer Ingelheim; Financial Interests, Personal, Other, Consultant compensated: Bristol Myers Squibb; Financial Interests, Personal, Other, Consultant compensated: GlaxoSmithKline; Financial Interests, Personal, Other, Consultant compensated: Janssen; Financial Interests, Personal, Other, Consultant compensated: MorphoSys; Financial Interests, Personal, Other, Consultant compensated: Novartis; Financial Interests, Personal, Other, Consultant compensated: Roche; Financial Interests, Personal, Other, Consultant compensated: Takeda; Financial Interests, Personal, Other, Honoraries for CME presentations: Amgen; Financial Interests, Personal, Other, Honoraries for CME presentations: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraries for CME presentations: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraries for CME presentations: Janssen; Financial Interests, Personal, Other, Honoraries for CME presentations: MSD; Financial Interests, Personal, Other, Honoraries for CME presentations: Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Bristol Myers-Squibb. T.N. Fehm: Financial Interests, Institutional, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche; Financial Interests, Institutional, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis; Financial Interests, Institutional, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pfizer; Financial Interests, Institutional, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Daiichi Sankyo; Financial Interests, Institutional, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca; Financial Interests, Institutional, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: MSD; Financial Interests, Institutional, Speaker’s Bureau, honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: TEVA; Financial Interests, Personal, Other, Travel grant: Daiichi Sankyo; Financial Interests, Personal, Other, Travel grant: Roche; Financial Interests, Institutional, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Roche; Financial Interests, Institutional, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Pfizer. D. Lüftner: Financial Interests, Personal, Other, Lectures: Amgen; Financial Interests, Personal, Other, Lectures: AstraZeneca; Financial Interests, Personal, Other, Lectures: Eli Lilly; Financial Interests, Personal, Other, Lectures: GSK; Financial Interests, Personal, Other, Lectures: Loreal; Financial Interests, Personal, Other, Lectures: MSD; Financial Interests, Personal, Other, Lectures: Mundipharma; Financial Interests, Personal, Other, Lectures: Mylan; Financial Interests, Personal, Other, Lectures: Novartis; Financial Interests, Personal, Other, Lectures: Pfizer; Financial Interests, Personal, Other, Lectures: Roche; Financial Interests, Personal, Other, Lectures: Teva; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Amgen; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Eli Lilly; Financial Interests, Personal, Other, Support for attending meetings and/or travel: GSK; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Loreal; Financial Interests, Personal, Other, Support for attending meetings and/or travel: MSD; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Mundipharma; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Mylan; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Novartis; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Pfizer; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Teva. C. quiering: Financial Interests, Personal, Full or part-time Employment, Employee of Novartis Pharma GmbH (Study Sponsor): Novartis Pharma GmbH . M. Reinisch: Financial Interests, Institutional, Writing Engagements, Medical writing: Novartis; Financial Interests, Personal, Other, Honoraria for lectures and presentations: Novartis; Financial Interests, Personal, Other, Honoraria for lectures and presentations: Lilly; Financial Interests, Personal, Other, Honoraria for lectures and presentations: Pfizer; Financial Interests, Personal, Other, Travel support: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Lilly. All other authors have declared no conflicts of interest.