Impact of cancer related fatigue on quality of life of 1,262 patients with breast cancer receiving chemotherapy: A URCC NCORP nationwide phase III RCT.

12130 Background: Cancer-related fatigue (CRF) is one of the most common and debilitating symptoms reported by cancer patients, significantly impairing quality of life (QoL) across physical, functional, emotional, and social domains. Despite its prevalence, limited data exist quantifying how rapid changes in CRF after a single chemotherapy cycle influence QoL. We aim to evaluate if rapid clinically meaningful changes in CRF post chemotherapy impact QoL in breast cancer patients. Methods: This Phase III RCT (NCT03367572) enrolled chemotherapy-naïve breast cancer patients across 21 NCORP practices receiving high/moderate emetogenic chemotherapy. CRF was assessed at baseline and post chemotherapy cycle 1 (n = 1,262) using a four-day home diary, with maximum fatigue change as the primary outcome. For analysis, the CRF variable was dichotomized into two categories: a clinically significant increase (≥3 points) and less than a 3-point increase. QOL was measured with FACT-G and its subscales: emotional (EWB), functional (FWB), physical (PWB), and social (SWB). ANCOVA and Cohen’s d effect size (ES) evaluated whether clinically meaningful CRF changes predicted QOL changes across cycles. Results: Among 1,262 patients with valid fatigue scores, 74.8% experienced increased CRF after cycle 1, with 53.2% reporting a ≥3-point increase and a mean increase of 2.9 points for the group. Clinically significant increases in CRF strongly impacted quality of life (QOL), as reflected in FACT-G Total Score changes post-cycle 1 (≥3: −12.4 vs < 3: −4.7; mean difference: 7.7, p < 0.001, ES: 0.74), exceeding the clinically meaningful threshold of > 5 points. Analysis of the subscales revealed PWB with the largest changes of 4.8 (≥3: −X vs < 3: −X; p < 0.001, ES: 1.00). FWB changes were 2.1 (≥3: −X vs < 3: −X; p≤0.0001, ES: 0.48) and EWB changes were 0.7 (≥3: −X vs < 3: −X; p < 0.001, ES: 0.26). CRF did not significantly impact SWB. Notably, many of these subscale changes surpassed the clinically meaningful threshold of > 2 points. Conclusions: This study underscores the rapid onset and significant impact of CRF on QoL in breast cancer patients receiving chemotherapy. Clinically meaningful increases in CRF, even after a single chemotherapy cycle, were predictive of substantial declines in QoL, particularly in physical and functional well-being. These results emphasize the urgent need for targeted fatigue management strategies, such as tailored interventions addressing physical and functional domains, to improve patient outcomes. Clinical trial information: NCT03367572 .