267P AB-ITALY: The impact of drug-drug interaction on abemaciclib treatment in Italian real world experience

Abstract

Abemaciclib demonstrated a clinical benefit in women affected by HR+/HER2- metastatic breast cancer (mBC). Drug-drug interactions (DDIs) can lead to a reduced treatment efficacy or increased toxicity. Drug-PIN® (Personalized Interactions Network) is a tool recognizing the crucial role of multiple interactions between active and/or pro-drug forms combined with biochemical and demographic patient data. This retro-prospective study aimed to evaluate outcomes, toxicities and DDIs of abemaciclib combined with hormone therapy in a real-world setting. Patients (pts) from 12 referral hospitals in Italy, affected by HR+/HER2- mBC who received abemaciclib were included. Availability of clinical data about comorbidities, concurrent medications, outcomes were inclusion criteria. Drug-PIN® was used to define the Drug-PIN score and Drug-PIN tier (green, yellow, dark yellow, orange, and red) for each pt. Univariate and multivariate analysis were performed to identify early predictors of patients PFS, toxicity or best response (BR). A total of 173 pts were included. Abemaciclib was administered in combination with fulvestrant or with aromatase inhibitors in 92 and 81 pts, respectively. Overall response rate (ORR) was 62.8%. The median PFS was 28.8 months.The most common toxicities were diarrhoea, asthenia and neutropenia in 63%,49%,49% of pts respectively. Median Drug-PIN score was 3.25 (range 0 -114.8) and 150, 6, 8, 6 and 3 pts were in the green, yellow, dark yellow, orange and red tier, respectively. At the univariate analysis, the number of drugs (p=0.003), the best response (p<0.0001), the high values of Drug-PIN score (p=0.015) and the Drug-PIN tier (from dark yellow to red, p=0.039) were associated with decreased PFS. Correcting for significant variables found at univariate analysis, only the association between BR (p<0.0001), Drug-PIN tier (dark yellow to red, p=0.007) and decreased PFS were confirmed at the multivariate analysis (p<0.0001). Our study suggests that the concomitant use of multiple drugs is associated with higher toxicity in pts affected by mBC treated with abemaciclib. Moreover, a statistically significant association between decreased PFS and high Drug-PIN score was shown.