211P Drug-drug interactions and their impact on clinical outcomes and adverse events in hormone receptor (HR)+/HER2- advanced breast cancer patients treated with ribociclib + letrozole: Insights from the BioltaLEE trial

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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. 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). 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). 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.

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