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

Shadab A Rahman; Hanneke Poort; Deborah Schrag; Stephanie C Tung; Eric S Zhou; Aleta Wiley; Lauren B Finkelstein; Elkhansaa Elguenaoui; Moira Nolan; Erica L Mayer; Hadine Joffe

doi:10.1093/oncolo/oyae316

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

Oncologist. 2024 Dec 19:oyae316. doi: 10.1093/oncolo/oyae316. Online ahead of print.

Authors

Shadab A Rahman^{1

2

3}, Hanneke Poort⁴, Deborah Schrag^{5

6}, Stephanie C Tung^{5

6

7}, Eric S Zhou^{5

6}, Aleta Wiley⁷, Lauren B Finkelstein⁷, Elkhansaa Elguenaoui⁷, Moira Nolan⁷, Erica L Mayer^{5

6}, Hadine Joffe^{1

3

5

6

7}

Affiliations

¹ Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, United States.
² Division of Sleep and Circadian Disorders, Department of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA 02115, United States.
³ Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.
⁴ Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, MA 02115, United States.
⁵ Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States.
⁶ Harvard Medical School, Boston, MA 02115, United States.
⁷ Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States.

PMID: 39703168
DOI: 10.1093/oncolo/oyae316

Abstract

Objectives: 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.

Keywords: activity; cyclin-dependent kinase inhibitors; fatigue; metastatic breast cancer; sleep.