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哌柏西利属于细胞有丝分裂周期蛋白依赖型激酶4/6（CDK4/6）抑制剂，可以阻断雌激素受体阳性乳腺癌细胞的分裂和增殖。根据国际多中心双盲Ⅲ期随机对照研究PALOMA-3的结果，氟维司群+哌柏西利与氟维司群＋安慰剂相比，对于既往内分泌治疗失败的激素受体阳性HER2阴性转移性乳腺癌，中位无进展生存显著延长（9.5比4.6个月），复发死亡风险减少54%（风险比：0.46，P<0.0001）。 2019年1月10日，SAGE旗下奥克兰《乳腺癌》在线发表荷兰圣安东尼医院、乌得勒支大学的真实世界研究报告，评定了哌柏西利＋内分泌治疗对于激素受体阳性HER2阴性晚期或转移性乳腺癌既往内分泌治疗失败后患者的实际有效性和耐受性，并与PALOMA-3临床研究结果进行了比较。 该单中心队列观察研究对2016年9月1日～2018年4月1日圣安东尼医院所有激素受体阳性HER2阴性晚期或转移性乳腺癌既往内分泌治疗失败后接受哌柏西利治疗的患者进行回顾，根据电子病历收集患者个人数据。主要研究结局为无进展生存、疾病进展前不良事件所致治疗永久停止。次要研究结局为所有（严重）不良事件发生率，以及减量率、停药率、疗程推迟率及其原因。 结果，共计46例患者，截至2018年10月1日，中位随访13.0个月。总体而言，实际临床实践的中位无进展生存为10.0个月（95%置信区间：4.9～15.1），而PALOMA-3为9.5个月（95%置信区间：9.2～11.0）。16例不符合PALOMA-3研究入组条件标准患者的中位无进展生存较短，为5.5个月（95%置信区间：4.7～6.4）。 两例患者由于不良事件停止治疗。中性粒细胞减少为最常见的3～4级不良事件，但是无发热性中性粒细胞减少事件。大多数不良事件通过哌柏西利剂量调整进行管理。根据这些调整，临床实践与PALOMA-3相比，疗程推迟率较高、减量率较低、停药率较低（分别为59%比36%、22%比34%、9%比54%）。 因此，根据该研究结果，实际临床实践与PALOMA-3临床研究结果相比，哌柏西利的有效性和耐受性相似。虽然剂量调整存在差异，但是该患者人群的疗效相似。 不过，该荷兰单中心队列观察回顾研究仅46例患者，号称“真实世界研究”，这个“世界”似乎小了一些。 相关阅读 Breast Cancer (Auckl). 2019 Jan 10;13:1178223418823238. Real-World Effectiveness of Palbociclib Versus Clinical Trial Results in Patients With Advanced/Metastatic Breast Cancer That Progressed on Previous Endocrine Therapy. Bui TBV, Burgers DM, Agterof MJ, van de Garde EM. St. Antonius Hospital, Utrecht/Nieuwegein, The Netherlands; Utrecht University, Utrecht, The Netherlands. OBJECTIVE: The aim of this study was to assess the real-world effectiveness and tolerability of palbociclib combined with endocrine therapy for the treatment of hormone receptor positive (HR-positive), human epidermal growth factor receptor 2 negative (HER2-negative), advanced/metastatic breast cancer that progressed on previous endocrine therapy, and to compare these results with the outcomes of the PALOMA-3 clinical trial. METHODS: This study was a retrospective observational cohort study including all patients who started with palbociclib in the St. Antonius Hospital between September 1, 2016 and April 1, 2018 for the treatment of HR-positive, HER2-negative advanced/metastatic breast cancer that progressed on previous endocrine therapy. Individual patient data were collected from electronic medical records. Primary study outcomes were progression-free survival (PFS) and the number of permanent treatment discontinuations before disease progression due to adverse events (AEs). Secondary outcomes were the frequency of all (serious) AEs and the frequency of and reasons for dose reductions, -interruptions and cycle delays. RESULTS: A total of 46 patients were studied with a median follow-up of 13.0 months. Overall, the median PFS in real-world clinical practice was 10.0 months (95% confidence interval (CI) 4.9-15.1), compared with 9.5 months in PALOMA-3 (95% CI 9.2-11.0). Two patients discontinued treatment because of AEs. Neutropenia was the most frequent grade 3-4 AE, but with no febrile neutropenia events. Most AEs were managed with palbociclib dose modifications. Regarding these modifications, more cycle delays, less dose reductions, and less dose interruptions occurred in clinical practice compared with PALOMA-3 (59 vs 36%, 22 vs 34%, and 9 vs 54%, respectively). Patients who did not meet the PALOMA-3 study eligibility criteria (n = 16) showed a lower median PFS of 5.5 months (95% CI 4.7-6.4). CONCLUSIONS: The effectiveness and tolerability of palbociclib in real-world clinical practice corresponded well with the results obtained in the PALOMA-3 clinical trial. Despite the differences in dose modifications, this study suggests that there is no efficacy-effectiveness gap in this patient population. KEYWORDS: clinical practice; efficacy-effectiveness gap; metastatic breast cancer; palbociclib; real-world; tolerability PMID: 30675102 PMCID: PMC6330732 DOI: 10.1177/1178223418823238 |
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