Real-world experience and clinical impact of drug-drug interactions in HR+/HER2- advanced breast cancer patients treated with abemaciclib plus endocrine therapy: the AB-ITALY study

BACKGROUND Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2- advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to a reduced treatment efficacy or increased toxicity. This retro-prospective study aimed to evaluate outcomes, DDIs’ impact and toxicities of abemaciclib combined with endocrine therapy in a real-world setting. METHODS Patients from 12 referral Italian hospitals with HR+/HER2- aBC who received abemaciclib were included. Clinical data about comorbidities, concurrent medications, outcomes and adverse events (AE) were collected. Drug-PIN® (Personalized Interactions Network) is a tool recognizing the role of multiple interactions between active and/or pro-drug forms combined with biochemical and demographic patient data. The software was used to define the Drug-PIN score and Drug-PIN tier (green, yellow, dark yellow and red) for each patient. Univariate and multivariate analysis were performed to identify predictors of patients PFS or toxicity. RESULTS One hundred seventy-three patients were included. 13% of patients had > 75years. Overall response rate (ORR) was 63%. The median PFS (mPFS) of the overall population was 22 months (mo), while mOS was not reached. Patients treated with abemaciclib in combination with AI and fulvestrant had a mPFS of 36 and 19 mo, respectively. The most common toxicities were diarrhoea, asthenia and neutropenia detected in 63%,49%,49% of patients, respectively. The number of concomitant medications and comorbidities were not associated with survival outcomes (22 vs 17 mo, p = 0.068, p = 0.99). Drug-PIN tier from dark yellow to red and Drug-PIN score > 12 were associated with shorter PFS compared to no/low risk DDIs and score < 12 (15 vs 23, p = 0.005, p = 0.0017). Drug interaction was confirmed as an independent biomarker in a multivariate model (p = 0.02). No difference in any-grade AE, severe toxicities and diarrhoea was detected among different age subgroups. No association was found between Drug-PIN score or Drug-PIN tier and overall toxicity (p = 0.44), severe AEs (p = 0.11) or drug reduction (p = 0.27) CONCLUSIONS Efficacy and safety of abemaciclib plus ET were confirmed in a real-world setting, even in elderly population and patients with comorbidities. Evaluation of DDIs with Drug-PIN appear to be an independent predictor of PFS.