Clinical impact of drug-drug interactions on abemaciclib in the real-world experience of AB-ITALY study

• Published in: NPJ breast cancer 2024-07, Vol.10 (1), p.58-10, Article 58
• Main Authors: Scagnoli, Simone, Pisegna, Simona, Toss, Angela, Caputo, Roberta, De Laurentiis, Michelino, Palleschi, Michela, de Giorgi, Ugo, Cortesi, Enrico, Fabbri, Agnese, Fabi, Alessandra, Paris, Ida, Orlandi, Armando, Curigliano, Giuseppe, Criscitiello, Carmen, Garrone, Ornella, Tomasello, Gianluca, D’Auria, Giuliana, Vici, Patrizia, Ricevuto, Enrico, Domati, Federica, Piombino, Claudia, Parola, Sara, Scafetta, Roberta, Cirillo, Alessio, Taurelli Salimbeni, Beatrice, Di Lisa, Francesca Sofia, Strigari, Lidia, Preissner, Robert, Simmaco, Maurizio, Santini, Daniele, Marchetti, Paolo, Botticelli, Andrea
• Format: Article
• Language: English
• Subjects: 692/4028/67/1059/602; 692/4028/67/1347; 692/4028/67/1857; 692/700/155; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Cell Biology; Drug interactions; Human Genetics; Older people; Oncology; Patients; Toxicity
• ISSN: 2374-4677; 2374-4677
• DOI: 10.1038/s41523-024-00657-z

Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2− advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to 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. 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 analyses were performed to identify predictors of patients’ PFS or toxicity. One hundred seventy-three patients were included. 13% of patients had >75years. The overall response rate (ORR) was 63%. The general population’s median PFS (mPFS) was 22 months (mo), while mOS were 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 diarrhea, asthenia, and neutropenia detected in 63%,49%, and 49% of patients. 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