Abstract 211P
Background
Drug-drug Interactions (DDIs) are a major public health issue and may cause unexpected changes in drug efficacy and AEs. We evaluated the impact of DDIs on clinical outcomes and adverse events (AEs) in a post-hoc analysis of the BioItaLEE trial, which enrolled postmenopausal HR+/HER2- advanced breast cancer patients (pts) treated with upfront ribociclib plus letrozole.
Methods
Data of pts were collected from eCRF. Drug-PIN®(DP) is a tool that identifies DDI combined with biochemical and clinical data. DP produces a numerical score (DP score) and a tier (green - G, yellow - Y, dark yellow - DY and red -R) according to increasing DDIs risk. Median cut-off point was used for DP score. We performed a post-hoc analysis on the association of DDIs with clinical outcomes and the most common AEs. The multivariate analysis (MVA) was performed using the prespecified stratification factors (recurrent vs de novo, tumor type, tumor burden and visceral disease).
Results
DDIs analysis was performed on the 287 pts enrolled in the trial. The median DP score was 10 (range 6-220). The mPFS was 20.7 months (mo) in DP score >10 and 28.0 mo in ≤10 (HR 1.59, p=0.02). DP tier was G in 203 (71%), Y in 57 (20%), DY in 15 (5%) and R in 12 (4%) pts respectively. mPFS was 28.0, 22.7, 19.4 and 13.8 mo in pts with G, Y, DY and R tiers, respectively (p=0.04). The MVA showed that DP score and tier were independently associated with shorter PFS (DP score ≤10 vs >10, HR 1.59, p=0.02; DP tier G vs non-G, HR 1.75, p<0.01). No association was detected between DP and all grades neutropenia, all grades QT prolongation and all grades ALT increase. Finally, all grades AST elevation was more frequent in pts with DP score ≤10 (23% vs 12%, HR 0.39, 95%CI 0.20-0.79, p=0.02).
Conclusions
pts with high-risk DDIs (high DP score or tier) have a shorter PFS compared to pts with no/low DDIs. No difference in AEs was detected among the groups, except for AST elevation. Our study highlights the importance of evaluating DDI and of therapeutic reconciliation to maximize oncological treatment efficacy in this setting and lays the foundations for further research.
Clinical trial identification
NCT03439046.
Legal entity responsible for the study
Novartis Farma S.p.A.
Funding
Novartis Farma S.p.A.
Disclosure
A. Botticelli: Financial Interests, Personal, Invited Speaker: Lilly, Novartis, MSD, BMS, Pierre Fabre, Daiichi Sankyo, AstraZeneca, Amgen; Financial Interests, Personal and Institutional, Principal Investigator: Gilead, Daiichi Sankyo, AstraZeneca, Roche, MSD. G. Bianchini: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer, Roche, Amgen, MSD, Chugai, Eisai, Gilead, Seagen, Exact Science, Roche, MSD, Gilead; Financial Interests, Personal, Other, Consultancy: AstraZeneca, Daiichi Sankyo, Roche, MSD, Gilead, Sanofi; Financial Interests, Personal, Invited Speaker: Lilly, Roche, AstraZeneca, Daiichi Sankyo, MSD, Chugai, Eisai, Gilead, Seagen, Neopharm Israel; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche, Pfizer, MSD, Chugai, Novartis, Gilead, Daiichi Sankyo; Financial Interests, Personal and Institutional, Invited Speaker: Roche, Novartis, Lilly, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Gilead, Pfizer, Daiichi Sankyo, Lilly, MSD, Novartis; Non-Financial Interests, Leadership Role, Head of Traslational Research: Fondazione Michelangelo. L. Malorni: Financial Interests, Personal, Advisory Role, Steering Committee of the trial: Novartis; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Advisory Board: Pfizer, Seagen. A. Zambelli: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo, Gilead, MSD, Exact Science. F. Puglisi: Financial Interests, Institutional, Research Grant: AstraZeneca, Eisai, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Celgene, Eisai, Lilly, Exact Science, Gilead, MSD, Pierre Fabre, Pfizer, Roche, Seagen, Viatris; Financial Interests, Personal, Invited Speaker: Novartis. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed S.r.l.; Financial Interests, Personal, Invited Speaker, Lecture: Ipsen; Financial Interests, Personal, Advisory Board, Her2+ and TN breast cancer: Roche; Financial Interests, Personal, Invited Speaker, Consultancy for TNBC text: Roche; Financial Interests, Personal, Advisory Board, denosumab: Amgen; Financial Interests, Personal, Advisory Board, Early and metastatic BC: Eli Lilly; Financial Interests, Personal, Invited Speaker, CDK4-6 inhibitors: Eli Lilly; Financial Interests, Personal, Advisory Board, tucatinib: Seagen Int; Financial Interests, Personal, Advisory Board, Oncotype dx: Exact sciences, Havas life; Financial Interests, Personal, Advisory Board, Neratinib: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Internal training: MSD; Financial Interests, Personal, Invited Speaker, Educational meetings: Accademia Nazionale Medicina; Financial Interests, Personal, Invited Speaker, Author for BC text: Pensiero Scientifico Editore; Financial Interests, Personal, Advisory Board, Breast cancer: Uvet; Financial Interests, Personal, Other, Author slide kits and interviews: Think2it; Financial Interests, Personal, Advisory Board, Palbociclib: Pfizer; Financial Interests, Personal, Invited Speaker, Breast cancer: Aristea, Meeting S.r.l.; Financial Interests, Personal, Other, Author slide kits: Forum service; Financial Interests, Personal, Other, Author text about biosimilars: Edizioni Minerva Medica; Financial Interests, Personal, Other, consultant: Kardo S.r.l.; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over S.r.l.; Financial Interests, Personal, Invited Speaker: Prex S.r.l., Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca, Agendia, Gilead, GSK, Eisai, Stemline Menarini; Financial Interests, Personal, Other, Interview: Infomedica S.r.l.; Financial Interests, Personal, Other, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Personal, Other, Consultancy: Eli Lilly, Gilead; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Financial Interests, Institutional, Invited Speaker: Gilead, Seagen; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. M.A. Colleoni: Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Leadership Role, CO-Chair Scientific Committee: International Breast Cancer Study Group. F. Montemurro: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Advisory Board: Novartis, Pierre Fabre, AstraZeneca, Daiichi Sankyo, Lilly, Seagen, MSD. G.V. Bianchi: Financial Interests, Personal, Advisory Board: Roche, Lilly, Novartis, Seagen, AstraZeneca, MSD. M.B. Suter: Financial Interests, Personal, Full or part-time Employment: Novartis. S. Scagnoli: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Lilly, Daiichi Sankyo, Pierre Fabre; Financial Interests, Personal, Advisory Board: Lilly, AstraZeneca. P. Marchetti: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Eisai, Incyte, Meck, Novartis, Pierre Fabre, Pfizer, Roche; Financial Interests, Personal, Advisory Board: BMS, Roche, Genentech, MSD, Novartis, Amgen, Merck Serono, Pierre Fabre, Incyte, AstraZeneca, Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Incyte, Roche, Lilly, Merck, Novartis, Nanostring Technologies, Pierre Fabre, Pfizer, Takeda. M. De Laurentiis: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, AstraZeneca, Roche, Eisai, Lilly, Pierre Fabre, Daiichi Sankyo, Menarini, Gilead, Seagen, GSK; Financial Interests, Personal, Advisory Board: Pfizer, Novartis, AstraZeneca, Roche, Eisai, Lilly, MSD, Pierre Fabre, Daiichi Sankyo, Menarini, Gilead, Seagen, GSK. All other authors have declared no conflicts of interest.