Efficacy and safety of anamorelin in patients with non–small cell lung cancer and cancer cachexia undergoing chemoimmunotherapy: A real-world prospective cohort study (SPIRAL-ANA).

8592 Background: The efficacy and safety of combining anamorelin with chemoimmunotherapy for non–small cell lung cancer (NSCLC) complicated by cancer cachexia remain unclear. This study aims to clarify the potential clinical benefits of combining anamorelin with standard first-line treatment in this challenging patient subpopulation. Methods: We prospectively enrolled patients with advanced NSCLC who had cancer cachexia and were scheduled to initiate anamorelin together with chemoimmunotherapy. Cancer cachexia was defined according to the eligibility criteria for anamorelin administration in Japan. Anamorelin is indicated for patients with body weight loss of ≥5% within the previous 6 months and with anorexia, who meet at least two of the following criteria: 1) fatigue or malaise, 2) generalized muscle weakness, or 3) C-reactive protein level >0.5 mg/dL, or albumin level <3.2 g/dL, or hemoglobin level <12 g/dL. Progression-free survival (PFS) from start of chemoimmunotherapy was the primary endpoint. Results: Overall, 123 patients were enrolled, of whom 118 comprised the safety analysis set and 114 comprised the full analysis set. The median duration of anamorelin treatment was 13.15 weeks. Median age, body weight, and body mass index were 73 years (range: 42–89 years), 53.2 kg (range: 32.5–79.4 kg), and 20.2 kg/m 2 (range: 15.0–29.1 kg/m 2 ), respectively. Among these patients, 20 (17.5%) had an Eastern Cooperative Oncology Group performance status of 2. At week 12, 62 patients (54.4%) were still being treated with anamorelin. The median PFS and overall survival (OS) were 6.2 months and 18.5 months, respectively, and the study did not meet the prespecified PFS endpoint. In a 12-week landmark analysis stratified by cachexia status at week 12, OS was significantly longer in patients who had achieved cachexia improvement by week 12 than in those who remained cachectic (19.9 months versus 7.1 months, log-rank p = 0.0098; hazard ratio for death, 2.19; 95% confidence interval, 1.19–4.02). The safety profile was manageable, with grade ≥3 neutropenia and hyperglycemia occurring in 31.4% and 5.1% of patients, respectively, and no deaths were considered related to anamorelin. Conclusions: In this prospective real-world cohort of patients with NSCLC and cancer cachexia receiving first-line chemoimmunotherapy, anamorelin was associated with a manageable safety profile but did not achieve the primary endpoint of PFS prolongation. Cachexia improvement at week 12 was observed in a substantial proportion of patients and was associated with longer OS. These findings suggest that the clinical value of anamorelin in this setting may lie in facilitating cachexia improvement.