Cancer cachexia and symptomatic toxicity among 706 older adults with advanced cancer receiving treatment: A URCC NCORP nationwide study.

12067 Background: Cancer cachexia is a severe wasting condition characterized by rapid weight loss. Its impact on symptomatic toxicity is poorly defined in geriatric oncology populations, who are at high risk for cachexia. Symptomatic toxicity is central to treatment tolerability and is linked to poor quality of life, functional decline, and reduced survival. We evaluated whether cachexia is associated with symptomatic toxicity before and during high-risk cancer treatment in older adults with advanced cancer. Methods: In a randomized controlled trial (GAP70+; NCT02054741), adults aged ≥70 with stage III or IV solid tumors or lymphoma were recruited prior to starting a new cancer treatment from 40 community oncology practices affiliated with the University of Rochester NCI Community Oncology Research Program (NCORP) Research Base. Cachexia (≥5% weight loss in the past six months) was assessed at baseline via Mini Nutritional Assessment. Symptoms (fatigue, insomnia, pain, anorexia, dyspnea, concentration problems, nausea, sensory neuropathy, constipation, diarrhea) were assessed at baseline and 3 months using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Symptoms were measured as mild, moderate, severe, or very severe. Log-binomial regression models examined associations of cachexia with baseline and three-month incident symptoms (baseline-adjusted method). Results: Among 706 participants (mean age: 77.2 years; 57% male; 59% gastrointestinal or lung cancer; 26% received prior chemotherapy), 42% had cachexia at baseline. Participants with cachexia were more likely than those without to report severe/very severe baseline symptoms (56% vs. 35%, chi-square p < 0.01). Analyses show that those with cachexia were 2-3 times more likely to report baseline severe/very severe anorexia (Risk Ratio (RR): 3.64, 95%CI: 2.44 - 5.42), fatigue (RR: 2.28, 95%CI: 1.65 - 3.16), pain (RR: 2.03, 95%CI: 1.36 - 3.04), and constipation (RR: 2.02, 95%CI: 1.27 - 3.22), as well as moderate or worse nausea (RR: 1.72, 95%CI: 1.16 - 2.55) and concentration problems (RR: 1.56, 95%CI: 1.03 - 2.39; all p < 0.05). Baseline cachexia was also associated with the development of severe/very severe anorexia (RR: 1.88, 95%CI: 1.20 - 2.94; p < 0.01) from baseline to 3-months. Conclusions: Nearly half of older adults with advanced cancer initiating a treatment regimen have cachexia. We demonstrate via PRO-CTCAE that cachexia is associated with a significantly worse pre-treatment symptom burden. Cachexia was linked to severe anorexia before and after treatment initiation, highlighting a critical gap in supportive care. As novel agents targeting appetite and cachexia enter phase III trials, further research is needed to establish the temporal course of cachexia-related symptoms to identify ideal timing and candidates for therapeutic strategies. Clinical trial information: NCT02054741 .