Kubilay Tolunay Pınar, Kurt İnci Bediz, Usta Şura, Topkaç Ali, Karabuğa Berkan, Aydemir Ergin, Öner İrem, Akay Hacan Büşra, Ateş Öztürk, Karaçin Cengiz, Yalçıntaş Arslan Ülkü
Department of Medical Oncology, Ankara University School of Medicine, Ankara 06590, Turkey.
Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara 06200, Turkey.
Curr Oncol. 2024 Nov 22;31(12):7426-7436. doi: 10.3390/curroncol31120548.
BACKGROUND/OBJECTIVES: Dose reductions in CDK4/6 inhibitors, such as ribociclib and palbociclib, are often necessary due to treatment-related toxicities in patients with advanced breast cancer. This study aims to evaluate the impact of the timing of dose reductions on progression-free survival (PFS) and overall survival (OS) in a real-world cohort.
This single-center, retrospective study included patients treated with ribociclib or palbociclib between 2019 and 2023 at a cancer center in Turkey. Dose reductions due to drug-related toxicities were recorded, and survival outcomes were analyzed. Patients were categorized based on the timing of dose reductions: within the first 3 months (early) and after 3 months (late).
Among 392 patients (mean age 57.13 years), 16.8% had dose reductions within 3 months, 21.7% had late dose reductions, and 61.5% had no dose reductions. The mPFS was 14.26 months for early dose reductions, 33.12 months for late dose reductions, and 20.6 months for no dose reductions ( < 0.001). The mOS was 37.12 months for early dose reductions, not reached for late dose reductions, and 57.76 months for no dose reductions ( < 0.001). Hematological toxicity, primarily neutropenia, was the most common cause of dose reductions. The ECOG performance status, line of therapy, and CDK4/6 inhibitor type were also significant predictors of PFS and OS.
Early dose reductions in CDK4/6 inhibitors negatively affect PFS and OS, highlighting the importance of maintaining treatment intensity in the first 3 months. However, late dose reductions do not negatively affect progression-free survival (PFS) or overall survival (OS), with late dose reductions associated with better outcomes. Prospective studies in larger patient populations will further clarify our knowledge on this subject.
背景/目的：由于晚期乳腺癌患者存在与治疗相关的毒性，常常需要减少细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂（如瑞博西尼和哌柏西利）的剂量。本研究旨在评估在真实世界队列中，剂量减少时机对无进展生存期（PFS）和总生存期（OS）的影响。
这项单中心回顾性研究纳入了2019年至2023年期间在土耳其一家癌症中心接受瑞博西尼或哌柏西利治疗的患者。记录因药物相关毒性导致的剂量减少情况，并分析生存结果。根据剂量减少的时机对患者进行分类：在最初3个月内（早期）和3个月后（晚期）。
在392例患者（平均年龄57.13岁）中，16.8%在3个月内出现剂量减少，21.7%出现晚期剂量减少，61.5%未出现剂量减少。早期剂量减少患者的中位PFS为14.26个月，晚期剂量减少患者为33.12个月，未出现剂量减少患者为20.6个月（<0.001）。早期剂量减少患者的中位OS为37.12个月，晚期剂量减少患者未达到，未出现剂量减少患者为57.76个月（<0.001）。血液学毒性，主要是中性粒细胞减少，是剂量减少最常见的原因。东部肿瘤协作组（ECOG）体能状态、治疗线数和CDK4/6抑制剂类型也是PFS和OS的显著预测因素。
CDK4/6抑制剂的早期剂量减少对PFS和OS有负面影响，凸显了在最初3个月维持治疗强度的重要性。然而，晚期剂量减少对无进展生存期（PFS）或总生存期（OS）没有负面影响，晚期剂量减少与更好的结果相关。在更大患者群体中的前瞻性研究将进一步阐明我们对该主题的认识。
