The association of baseline fatigue and severe cancer treatment toxicity by comorbid conditions: A pooled analysis.

Abstract

11036 Background: Fatigue is commonly reported by patients with cancer. Patients who report fatigue are at greater risk of severe adverse events during treatment. However, it is unknown whether the relationship between baseline fatigue and toxicity risk persists after accounting for comorbid conditions. Methods: Data from 6 SWOG phase 2/3 clinical trials in advanced cancer (1999 to 2018) were pooled. Baseline fatigue (classified by 5-point Likert scale) was analyzed as any vs none. Patients were linked to Medicare claims by SSN, date of birth, and sex to identify comorbidities at study registration. Adverse events (AEs) were classified using the Common Terminology Criteria for Adverse Events. The primary outcome was severe (≥ grade 3) events. Odds ratios (ORs) were calculated using generalized estimating equations, clustered by study, and adjusted for age, sex, race, and obesity. Interaction tests between fatigue and each comorbidity were examined. Results: Among 1195 patients (median age, 73; 13.1% female; 11.8% Black; 74% prostate cancer), 629 (52.6%) had ≥1 severe AE. Among patients with ≥1 comorbid condition, those with any fatigue had a 132% (OR=2.32, 95% CI, 1.26-4.27, p=.007) increased risk of having severe AEs; among patients with no comorbidities, the association was nearly identical (OR=2.33, 95% CI, 1.51-3.60, p<.001; p-interaction=.97). Those with any fatigue had a twofold or greater risk of severe AEs across all comorbidities (Table). The association between fatigue and severe toxicity was greater for those with anemia (interaction p=.03) and those with depression (interaction p=.02). Conclusions: The association between baseline fatigue and severe treatment toxicity persisted after accounting for comorbid conditions, indicating baseline fatigue is an independent risk factor. The association was stronger among patients with anemia and those with depression, suggesting these conditions may amplify the risk of baseline fatigue. These findings support early identification of baseline fatigue and targeted supportive interventions for these high-risk populations. Association of baseline fatigue and severe toxicity by comorbid conditions. No comorbidity Comorbidity Comorbidity OR (95% CI) p-value OR (95% CI) p-value p-interaction Depression 2.24 (1.28-3.92) 0.005 4.32 (2.58-7.23) <0.0001 0.02 Anemia 2.15 (1.30-3.57) 0.003 3.05 (1.35-6.87) 0.007 0.03 Respiratory disorders (COPD, sleep apnea) 2.30 (1.35-3.94) 0.002 2.73 (0.99-7.55) 0.05 0.58 Hypothyroid 2.30 (1.34-3.95) 0.003 2.64 (1.33-5.23) 0.005 0.57 Diabetes 2.29 (1.35-3.89) 0.002 2.41 (1.24-4.71) 0.01 0.73 Hypertension 2.26 (1.36-3.78) 0.002 2.37 (1.25-4.50) 0.008 0.73 Cardiovascular disease 2.42 (1.39-4.22) 0.002 2.04 (1.15-3.63) 0.02 0.25 Autoimmune diseases 2.33 (1.34-4.04) 0.003 1.99 (1.15-3.43) 0.01 0.7 Any comorbidity (all comorbidities) 2.33 (1.51-3.60) <0.001 2.32 (1.26-4.27) 0.007 0.97