Factors associated with early cachexia in metastatic NSCLC: A nationwide Veterans Health Administration analysis.

e20681 Background: Cancer-associated cachexia is a frequent and often irreversible driver of morbidity in non-small cell lung cancer (NSCLC), affecting approximately 40% of patients (pts) and directly contributing to death in up to 20%. Yet effective preventative and therapeutic strategies remain lacking. We leveraged data from a nationwide Veterans Health Administration (VHA) cohort to identify clinical, demographic and disease-related factors associated with cachexia at the time of metastatic NSCLC diagnosis. Methods: We conducted an observational cohort study of Veterans with metastatic NSCLC diagnosed and treated within the VHA from January 1, 2010, to September 30, 2025. Cachexia was defined as ≥5% weight loss within 6 months prior to metastatic diagnosis, or ≥2% weight loss within 6 months prior to metastatic diagnosis in pts with body mass index 20 kg/m 2 . Multivariable logistic regression was used to identify factors independently associated with cachexia. Results: Among 23,107 Veterans with metastatic NSCLC (median age 69; 97.5% male; 19.1% non-Hispanic Black; 55.1% adenocarcinoma), cachexia was present in 9,921 pts (42.9%) at diagnosis. Cachexia occurred more frequently among non-Hispanic Black pts (22% vs. 17%, p < 0.001), those with high comorbidity burden (Charlson comorbidity index (CCI) ≥7: 40% vs. 28%, p < 0.001), and poorer performance status (ECOG ≥2: 53.7% vs. 40.9%, p < 0.001). Higher rates of cachexia were also observed in pts with liver metastases (22% vs. 19%, p < 0.001) and bone metastases (41% vs. 37%, p < 0.001), but not among those with brain metastases or lung-only metastases. In multivariable analysis, Black race (OR 1.38, 95% CI: 1.27-1.50, p < 0.001), squamous histology (OR 1.14, 95% CI: 1.06-1.23, p < 0.001), liver metastases (OR 1.16, 95% CI: 1.07-1.26, p < 0.001), and bone metastases (OR 1.18, 95% CI: 1.1-1.26, p < 0.001) were independently associated with increased odds of cachexia. Results were consistent in analyses restricted to pts with a single metastatic site. Cachexia was independently associated with worse survival after adjustment for metastatic sites, race, and comorbidity burden (OR 1.38, 95% CI: 1.33-1.42, p < 0.001). Conclusions: In this large national cohort of pts with metastatic NSCLC, cachexia was highly prevalent at diagnosis and independently associated with clinical and disease-related factors including race, histology, comorbidity burden, and specific sites of metastases. Importantly, cachexia remained independently associated with worse survival after adjustment for metastatic sites and patient characteristics. These findings highlight cachexia as a common, early, and clinically consequential condition in metastatic NSCLC and support the need for risk-stratified approaches to early cachexia identification, prevention, and therapeutic investigation.