Cardinal Health Specialty Solutions, 2515 McKinney Ave, Suite 1600, Dallas, TX, 75201, USA.
Pfizer, Inc., 235 East 42nd Street, New York, NY, 10017, USA.
Breast Cancer Res. 2018 May 2;20(1):37. doi: 10.1186/s13058-018-0958-2.
Rapidly evolving understanding of cancer biology has presented novel opportunities to translate that understanding into clinically relevant therapy. Palbociclib, a novel, first-in-class cyclin-dependent kinase (CDK) 4/6 inhibitor was approved in the USA in February 2015 for the treatment of advanced/metastatic breast cancer. We examined real-world evidence in the first year post approval to understand the clinical and demographic characteristics of patients treated with palbociclib in community oncology practices and the dosing, treatment, and complete blood count (CBC) monitoring patterns.
This was a retrospective observational study of structured data from a US electronic medical record (EMR) database. Female patients receiving palbociclib after 31 January 2015 were followed through 31 March 2016. Our methodological rules were constructed to aggregate drugs received according to the order in which they are given, i.e., identify the line of therapy as first, second, or third line, etc., using treatment order and course description fields from the EMR.
There were 763 patients initiating palbociclib who met the selection criteria. Of those, 612 (80.2%) received palbociclib concomitantly with letrozole. Mean follow up was 6.4 months and mean age at palbociclib initiation was 64 years. Of patients with a known starting dose (n = 417), 79.9% started on palbociclib 125 mg. Dose reductions were observed in 20.1% of patients. Percentages of patients according to line of therapy at initiation of palbociclib were first-line, 39.5%; second-line, 15.7%; third-line, 13.1%; and fourth-line therapy or later, 31.7%. On average, two CBC tests were conducted during the first cycle of palbociclib treatment. Overall, 74.6% of patients had a neutropenic event during follow up including 47.3% and 8.0% of patients with a grade 3 or 4 occurrence, respectively.
Real-world palbociclib use one year post US approval demonstrates a more heterogeneous patient population than that studied in the clinical trials with more than half of the patients receiving palbociclib plus letrozole in later lines of therapy. CBC testing rates suggested good provider compliance with monitoring guidelines in the USA prescribing information. The occurrence of grade 3 and 4 neutropenia (based on laboratory results) was consistent with the rates of grade 3 and 4 neutropenia in two phase-III studies (PALOMA-2, 56% and 10%; PALOMA-3, 55% and 11%, respectively). Understanding palbociclib utilization in real-world patients and how drug dosing and monitoring are performed aids in the understanding of safe and effective use of the drug.
癌症生物学的快速发展为将这一认识转化为具有临床意义的治疗方法提供了新的机会。帕博西尼（Palbociclib）是一种新型的、首创的细胞周期蛋白依赖性激酶（CDK）4/6 抑制剂，于 2015 年 2 月在美国获准用于治疗晚期/转移性乳腺癌。我们在批准后第一年进行了真实世界的证据研究，以了解在社区肿瘤学实践中接受帕博西尼治疗的患者的临床和人口统计学特征，以及给药方案、治疗和全血细胞计数（CBC）监测模式。
这是一项使用美国电子病历（EMR）数据库进行的回顾性观察性研究。2015 年 1 月 31 日以后接受帕博西尼治疗的女性患者，随访至 2016 年 3 月 31 日。我们的方法规则是根据给药顺序来聚合所接受的药物，即使用 EMR 中的治疗顺序和疗程描述字段，将治疗线识别为一线、二线等。
共有 763 名符合入选标准的患者开始使用帕博西尼。其中，612 名（80.2%）患者同时接受了来曲唑和帕博西尼治疗。中位随访时间为 6.4 个月，帕博西尼起始年龄为 64 岁。在已知起始剂量的患者中（n=417），79.9%的患者起始剂量为 125mg。观察到 20.1%的患者剂量减少。开始帕博西尼治疗时按治疗线划分的患者比例分别为一线治疗，39.5%；二线治疗，15.7%；三线治疗，13.1%；四线或以上治疗，31.7%。平均而言，在帕博西尼治疗的第一个周期中进行了两次全血细胞计数检查。总的来说，在随访期间，74.6%的患者发生中性粒细胞减少症，其中 47.3%和 8.0%的患者分别发生 3 级或 4 级中性粒细胞减少症。
在美国批准后一年的真实世界中使用帕博西尼表明，与临床试验中的患者群体相比，患者的异质性更大，超过一半的患者在后续治疗中接受了帕博西尼加来曲唑治疗。全血细胞计数检查率表明，美国处方信息中的监测指南得到了提供者的良好遵循。根据实验室结果，3 级和 4 级中性粒细胞减少症（基于实验室结果）的发生率与两项 III 期研究（PALOMA-2，56%和 10%；PALOMA-3，55%和 11%）中的 3 级和 4 级中性粒细胞减少症发生率一致。了解真实世界中帕博西尼的应用情况以及药物剂量调整和监测方式有助于了解药物的安全有效使用。
