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 <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 diarrhea were 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). The efficacy and safety of abemaciclib plus ET were confirmed in a real-world setting, even in the elderly population and patients with comorbidities. Evaluation of DDIs with Drug-PIN appears to be an independent predictor of PFS.

Clinical impact of drug-drug interactions on abemaciclib in the real-world experience of AB-ITALY study / Scagnoli, S.; Pisegna, S.; Toss, A.; Caputo, R.; De Laurentiis, M.; Palleschi, M.; de Giorgi, U.; Cortesi, E.; Fabbri, A.; Fabi, A.; Paris, I.; Orlandi, A.; Curigliano, G.; Criscitiello, C.; Garrone, O.; Tomasello, G.; D'Auria, G.; Vici, P.; Ricevuto, E.; Domati, F.; Piombino, C.; Parola, S.; Scafetta, R.; Cirillo, A.; Taurelli Salimbeni, B.; Di Lisa, F. S.; Strigari, L.; Preissner, R.; Simmaco, M.; Santini, D.; Marchetti, P.; Botticelli, A.. - In: NPJ BREAST CANCER. - ISSN 2374-4677. - 10:1(2024), pp. 1-10. [10.1038/s41523-024-00657-z]

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

Toss A.;Domati F.;Piombino C.;
2024

Abstract

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 <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 diarrhea were 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). The efficacy and safety of abemaciclib plus ET were confirmed in a real-world setting, even in the elderly population and patients with comorbidities. Evaluation of DDIs with Drug-PIN appears to be an independent predictor of PFS.
2024
10
1
1
10
Clinical impact of drug-drug interactions on abemaciclib in the real-world experience of AB-ITALY study / Scagnoli, S.; Pisegna, S.; Toss, A.; Caputo, R.; De Laurentiis, M.; Palleschi, M.; de Giorgi, U.; Cortesi, E.; Fabbri, A.; Fabi, A.; Paris, I.; Orlandi, A.; Curigliano, G.; Criscitiello, C.; Garrone, O.; Tomasello, G.; D'Auria, G.; Vici, P.; Ricevuto, E.; Domati, F.; Piombino, C.; Parola, S.; Scafetta, R.; Cirillo, A.; Taurelli Salimbeni, B.; Di Lisa, F. S.; Strigari, L.; Preissner, R.; Simmaco, M.; Santini, D.; Marchetti, P.; Botticelli, A.. - In: NPJ BREAST CANCER. - ISSN 2374-4677. - 10:1(2024), pp. 1-10. [10.1038/s41523-024-00657-z]
Scagnoli, S.; Pisegna, S.; Toss, A.; Caputo, R.; De Laurentiis, M.; Palleschi, M.; de Giorgi, U.; Cortesi, E.; Fabbri, A.; Fabi, A.; Paris, I.; Orland...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1367657
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