Fedele Palma, Landriscina Matteo, Moraca Lucia, Gadaleta-Caldarola Arianna, Cusmai Antonio, Giuliani Francesco, Chiuri Vincenzo, Giotta Francesco, Pinto Antonello, Mirisola Valentina, Gadaleta-Caldarola Gennaro
Oncology Unit, "Dario Camberlingo" Hospital, 72021 Francavilla Fontana, Italy.
U.O. Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy.
J Clin Med. 2024 Dec 6;13(23):7441. doi: 10.3390/jcm13237441.
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are the standard of care for hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer in combination with endocrine therapy. However, the real-world efficacy and safety of standard versus reduced doses in elderly patients remain unclear. This study aims to compare the clinical outcomes of standard versus reduced doses of CDK4/6 inhibitors in elderly patients with metastatic breast cancer. This multicenter retrospective cohort study included 158 patients aged ≥70 years diagnosed with HR+/HER2-negative metastatic breast cancer who received either standard or reduced doses of CDK4/6 inhibitors (Ademaciclib, Ribociclib, Palbociclib) as first-line therapy. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. PFS and OS were estimated using the Kaplan-Meier method, and comparisons between groups were performed using a log-rank test. Of the total population, 108 patients (68.4%) received the standard dose, and 50 patients (31.6%) received a reduced dose. The standard-dose group had significantly longer median PFS compared to the reduced-dose group (21.3 vs. 15.2 months, = 0.014), while the median OS did not differ significantly (37.2 vs. 37.2 months, = 0.103). Subgroup analyses revealed no significant differences in PFS or OS between standard and reduced doses for Ademaciclib and Ribociclib, while Palbociclib at standard dose showed superior PFS (21.9 vs. 12.7 months, = 0.029) and OS (50.5 vs. 28.6 months, = 0.026). The incidence of Grade 2-4 AEs was higher in the standard-dose group (74.2% vs. 56.8%, = 0.044). Dose reduction of CDK4/6 inhibitors, particularly Ademaciclib and Ribociclib, is a viable option in elderly patients, maintaining comparable OS outcomes to standard dosing while reducing the risk of adverse events. Palbociclib at standard dose may offer superior outcomes. These findings support personalized dosing strategies to optimize efficacy and tolerability in frail or elderly patients.
细胞周期蛋白依赖性激酶4和6（CDK4/6）抑制剂联合内分泌治疗是激素受体（HR）阳性/人表皮生长因子受体2（HER2）阴性转移性乳腺癌的标准治疗方案。然而，老年患者中标准剂量与降低剂量的实际疗效和安全性仍不明确。本研究旨在比较老年转移性乳腺癌患者中标准剂量与降低剂量的CDK4/6抑制剂的临床结局。这项多中心回顾性队列研究纳入了158例年龄≥70岁、诊断为HR阳性/HER2阴性转移性乳腺癌且接受标准剂量或降低剂量的CDK4/6抑制剂（阿贝西利、瑞博西尼、哌柏西利）作为一线治疗的患者。评估无进展生存期（PFS）、总生存期（OS）和不良事件（AE）。采用Kaplan-Meier方法估计PFS和OS，并使用对数秩检验进行组间比较。在总人群中，108例患者（68.4%）接受标准剂量，50例患者（31.6%）接受降低剂量。与降低剂量组相比，标准剂量组的中位PFS显著更长（21.3个月对15.2个月，P = 0.014），而中位OS无显著差异（37.2个月对37.2个月，P = 0.103）。亚组分析显示，阿贝西利和瑞博西尼的标准剂量与降低剂量在PFS或OS方面无显著差异，而标准剂量的哌柏西利显示出更好的PFS（21.9个月对12.7个月，P = 0.029）和OS（50.5个月对28.6个月，P = 0.026）。标准剂量组2-4级AE的发生率更高（74.2%对56.8%，P = 0.044）。降低CDK4/6抑制剂的剂量，尤其是阿贝西利和瑞博西尼，对老年患者是一个可行的选择，可维持与标准剂量相当的OS结局，同时降低不良事件风险。标准剂量的哌柏西利可能提供更好的结局。这些发现支持个性化给药策略，以优化体弱或老年患者的疗效和耐受性。
