Incidence of patient-reported fatigue developing on palbociclib and endocrine therapy for advanced HR+ HER2- breast cancer.

Journal: The Oncologist
Published:
Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Authors
Shadab Rahman, Hanneke Poort, Deborah Schrag, Stephanie Tung, Eric Zhou, Aleta Wiley, Lauren Finkelstein, Elkhansaa Elguenaoui, Moira Nolan, Erica Mayer, Hadine Joffe