Rahman Shadab A, Poort Hanneke, Schrag Deborah, Tung Stephanie C, Zhou Eric S, Wiley Aleta, Finkelstein Lauren B, Elguenaoui Elkhansaa, Nolan Moira, Mayer Erica L, Joffe Hadine
Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, United States.
Division of Sleep and Circadian Disorders, Department of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA 02115, United States.
Oncologist. 2025 Aug 4;30(8). doi: 10.1093/oncolo/oyae316.
Fatigue is a common nonhematologic toxicity of the CDK4/6 inhibitor palbociclib in metastatic breast cancer (MBC) patients with prevalence rates of clinician-rated all-grade and grade 3/4 fatigue of 39.2% and 2.5%, respectively. We prospectively assessed the incidence of fatigue emerging on palbociclib using patient-reported measures and explored potential predictors.
Eighty-eight patients with HR+ HER2- MBC without fatigue initiating palbociclib with endocrine therapy were assessed before and monthly across the initial 6 cycles. Clinically meaningful levels of patient-reported fatigue (Functional Assessment of Chronic Illness Therapy Fatigue Scale, FACIT-F < 34), severity of, and functional interference due to fatigue (NCI Patient-Reported Outcomes for CTCAE, PRO-CTCAE) were assessed. Hematologic and nonhematologic predictors were examined pretreatment and concurrent with fatigue assessments.
Patient-reported fatigue emerged in 21/88 patients [incidence rate 23.9% (95%CI, 15.4%-34.1%)] within 2.8 ± 1.7 treatment cycles. PRO-CTCAE-rated incidence rate of severe fatigue and fatigue interference was 14.8% (95%CI, 8.1%-23.9%) and 10.2% (95%CI, 4.8%-18.5%), respectively. Lower pretreatment absolute neutrophil count (ANC) levels predicted treatment-emergent fatigue (P =.01), but ANC levels on treatment did not (P =.78). Other pretreatment predictors were long sleep duration (P =.02) and low physical activity (trend, P =.07). Treatment-emergent fatigue was associated with objectively measured long sleep duration on treatment (P =.02), but not other measures (P ≥.35).
One-quarter of patients with HR+ HER2- MBC initiating palbociclib report rapidly emergent clinically meaningful fatigue, often with severe symptoms and functional interference. Treatment-emergent fatigue is associated with both pretreatment (lower ANC levels, longer sleep duration) and on-treatment (long sleep duration) hematologic and nonhematologic profiles.
疲劳是细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂哌柏西利在转移性乳腺癌（MBC）患者中常见的非血液学毒性，临床医生评定的所有级别和3/4级疲劳的发生率分别为39.2%和2.5%。我们使用患者报告的指标前瞻性评估了哌柏西利治疗期间出现疲劳的发生率，并探索了潜在的预测因素。
88例开始接受哌柏西利联合内分泌治疗且无疲劳症状的激素受体阳性（HR+）、人表皮生长因子受体2阴性（HER2-）MBC患者在初始6个周期治疗前及每月进行评估。评估患者报告的具有临床意义的疲劳水平（慢性病治疗功能评估疲劳量表，FACIT-F<34）、疲劳的严重程度以及疲劳导致的功能障碍（美国国立癌症研究所患者报告的不良事件通用术语标准，PRO-CTCAE）。在治疗前以及与疲劳评估同时检查血液学和非血液学预测因素。
21/88例患者（发病率23.9%[95%置信区间，15.4%-34.1%]）在2.8±1.7个治疗周期内出现患者报告的疲劳。PRO-CTCAE评定的严重疲劳和疲劳功能障碍的发病率分别为14.8%（95%置信区间，8.1%-23.9%）和10.2%（95%置信区间，4.8%-18.5%）。治疗前较低的绝对中性粒细胞计数（ANC）水平可预测治疗期间出现的疲劳（P = .01），但治疗期间的ANC水平则不能（P = .78）。其他治疗前预测因素为睡眠时间长（P = .02）和身体活动少（趋势，P = .07）。治疗期间出现的疲劳与治疗期间客观测量的睡眠时间长有关（P = .02），但与其他指标无关（P≥.35）。
四分之一开始接受哌柏西利治疗的HR+HER2-MBC患者报告迅速出现具有临床意义的疲劳，通常伴有严重症状和功能障碍。治疗期间出现的疲劳与治疗前（较低的ANC水平、较长的睡眠时间）以及治疗期间（较长的睡眠时间）的血液学和非血液学特征有关。
