Abemaciclib 对受 HR /HER2- 晚期乳腺癌 (aBC) 影响的女性具有临床益处。药物间相互作用 (DDI) 可导致治疗效果降低或毒性增加。这项回顾性前瞻性研究旨在评估 abemaciclib 联合内分泌治疗在现实环境中的结果、DDI 的影响和毒性。来自 12 家意大利转诊医院的接受 abemaciclib 治疗的 HR /HER2-aBC 患者被纳入研究。收集有关合并症、并发药物、结果和不良事件 (AE) 的临床数据。 Drug-PIN®（个性化交互网络）是一种工具，可识别活性药物和/或前药形式之间的多重相互作用，并结合生化和人口统计患者数据。该软件用于定义每位患者的 Drug-PIN 评分和 Drug-PIN 等级（绿色、黄色、深黄色和红色）。进行单变量和多变量分析以确定患者 PFS 或毒性的预测因素。一百七十三名患者被纳入其中。 13% 的患者年龄 >75 岁。总体缓解率 (ORR) 为 63%。一般人群的中位无进展生存期 (mPFS) 为 22 个月 (mo)，但尚未达到 mOS。使用 abemaciclib 联合 AI 和氟维司群治疗的患者的 mPFS 分别为 36 个月和 19 个月。最常见的毒性是腹泻、乏力和中性粒细胞减少，分别在 63%、49% 和 49% 的患者中检测到。合并用药和合并症的数量与生存结果无关（22 个月 vs 17 个月，p = 0.068，p = 0.99）。与无/低风险 DDI 和评分 <12 相比，从深黄色到红色的 Drug-PIN 等级和 Drug-PIN 评分 >12 与较短的 PFS 相关（15 vs 23，p = 0.005，p = 0.0017）。药物相互作用被证实为多变量模型中的独立生物标志物（p = 0.02）。不同年龄亚组之间未检测到任何级别的 AE、严重毒性和腹泻差异。未发现 Drug-PIN 评分或 Drug-PIN 等级与总体毒性 (p = 0.44)、严重 AE (p = 0.11) 或药物减少 (p = 0.27) 之间存在关联。 abemaciclib 加 ET 的有效性和安全性在现实环境中得到了证实，甚至在老年人和患有合并症的患者中也是如此。使用 Drug-PIN 评估 DDI 似乎是 PFS 的独立预测因子。© 2024。作者。

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. The Author(s).