Pooled analysis of association of baseline fatigue with severe toxic effects in patients with cancer receiving systemic therapy

Pooled analysis of 17 SWOG phase 2 and 3 trials conducted for 1990 to 2022 investigated the association of baseline patient-reported fatigue with the risk of subsequent cancer treatment-related adverse events. Among 7086 patients with prostate, lung, colorectal, lymphoma, breast, melanoma, ovarian, or pancreatic cancer, 103 738 AEs were reported. At baseline, 2771 participants (39.1%) reported some or more fatigue. Proportions with maximum AEs rated grade 3 or higher, grade 4 or higher, and grade 5 were 44.1%, 14.1%, and 0.9%, respectively. Compared with those reporting no or minimal fatigue, patients with some fatigue or more had higher risks of severe or worse toxic effects (OR 2.09; p<0.001), life-threatening or fatal toxic effects (OR 1.96; p<0.001), and fatal toxic effects (OR 2.35; p=0.03). A dose-response pattern was evident; patients reporting quite a lot or very much fatigue had an approximately 5-fold higher risk of fatal toxic effects. Findings were consistent across symptomatic, hematologic, and nonhematologic AE categories. The authors conclude that baseline patient-reported fatigue was associated with increased risk of cancer treatment-related toxic effects.