Abstract P4-09-01: Incidence of patient-reported fatigue developing in patients receiving palbociclib and endocrine therapy for advanced HR+ HER2- breast cancer
Authors: Rahman Shadab A , Mayer Erica L , Poort Hanneke , Schrag Deborah , Tung Stephanie C , Zhou Eric S , Wiley Aleta , Finkelstein Lauren , Elguenaoui Elkhansaa , Nolan Moira , Joffe Hadine 
Published: March 2022

Abstract
Background: Clinician-rated adverse event data from pivotal trials of the CDK4/6 inhibitor palbociclib (palbo) in patients (pts) with HR+ HER2- metastatic breast cancer (MBC) describe fatigue as a common non-hematologic toxicity. While palbo and endocrine therapy (ET) significantly improve outcomes compared to ET alone, in a pooled analysis of the PALOMA trials, rates of incident Common Terminology Criteria for Adverse Events (CTCAE) all-grade fatigue over 4.2 years of treatment approached 39.2%, with grade 3/4 at 2.5%. As these studies included only provider-rated CTCAE toxicity, it is important to quantify pts’ ratings of fatigue severity, which may differ from clinician assessments. Methods: Eligible pts with HR+ HER2- MBC, initiating standard-dose palbo with ET (aromatase inhibitor or fulvestrant), and without clinically meaningful fatigue prior to initiation of palbo, were followed for the 6 initial treatment cycles. The absence of baseline fatigue was established using the patient-reported Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F), a 13-item scale (range 0-52, lower score = more fatigue) validated against anemia to indicate clinically meaningful fatigue if FACIT-F score &lt;34. After screening and baseline assessments (several weeks apart), the FACIT-F was repeated during the 3rd week of 6 consecutive cycles. Pts also reported fatigue severity using the NCI Patient-Reported Outcomes for CTCAE (PRO-CTCAE; range 0-4; grade 3/4 = severe) when they completed the FACIT-F. The primary endpoint was new-onset fatigue (FACIT-F score &lt;34) after treatment initiation; the secondary endpoint was severe fatigue on the PRO-CTCAE fatigue severity item. Incident rate of fatigue was estimated based on frequencies (dichotomized FACIT-F scores &lt;34 vs. &gt;=34; PRO-CTCAE fatigue severity grade 3/4 vs. &lt;3). Rate of fatigue incidence on the FACIT-F in the presence of competing risks (e.g., disease progression or study burden) was estimated using the cumulative incidence function. Concurrently rated FACIT-F scores were compared between PRO-CTCAE severe and non-severe cases using linear mixed-models. Results: Of 115 pts enrolled (5/2018-1/2021), 88 were evaluable after excluding those not initiating palbo (n=3), without baseline data (n=13), or with clinically meaningful fatigue between screening and baseline (n=11). Mean (±SD) age was 59.4 ± 11.3, baseline FACIT-fatigue score was 44.4 ± 5.1, and follow-up duration was 5.8 ± 2.0 cycles. The majority (72%) were receiving palbo with letrozole. New-onset fatigue through the 6th treatment cycle was observed in 21 pts, translating to a fatigue incidence rate of 23.9% (95% CI 15.4% - 34.1%). The mean time to new-onset fatigue was 3.8 ± 1.7 treatment cycles. Those who withdrew early (n=26) completed data for 3.7 ± 2.1 treatment cycles; the cumulative incidence of fatigue at 4 treatment cycles was 18.2% (95% CI 10.9 - 26.9). Using the PRO-CTCAE, the incidence rate of severe fatigue was 14.8% (95% CI 8.1% - 23.9%). The mean FACIT-F score when PRO-CTCAE grade indicated severe fatigue was significantly lower (more fatigue) than when the PRO-CTCAE grade was non-severe (26.3 ± 5.1 vs. 44.8 ± 4.8, p&lt;0.0001). Conclusion: In pts with HR+ HER2- MBC initiating palbo and ET, approximately one-quarter develop fatigue within the first 6 cycles based on the FACIT-F, which associates significantly with a PRO-CTCAE severity grade 3/4. While direct comparison cannot be made between provider-rated CTCAE and patient-reported PRO-CTCAE, it is notable that the incidence of severe fatigue with PRO-CTCAE is higher than that observed with provider-rated CTCAE. Ongoing analyses will explore potential associations of factors (e.g., hematological, sleep, activity) with treatment-emergent fatigue developing on palbo and ET therapy.
Citation Format: Shadab A Rahman, Erica L Mayer, Hanneke Poort, Deborah Schrag, Stephanie C Tung, Eric S Zhou, Aleta Wiley, Lauren Finkelstein, Elkhansaa Elguenaoui, Moira Nolan, Hadine Joffe. Incidence of patient-reported fatigue developing in patients receiving palbociclib and endocrine therapy for advanced HR+ HER2- breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-09-01.