Efficacy and safety of anamorelin for cancer cachexia in patients with unresectable or recurrent gastric cancer: a multicentre, open-label, randomised controlled trial.

Background: Anamorelin, a ghrelin receptor agonist, has shown efficacy in lung cancer cachexia. We conducted the first randomized controlled trial to evaluate its effects in gastric cancer cachexia. Methods: In this multicenter, open-label randomized controlled trial conducted across 10 hospitals in Japan, patients with unresectable or recurrent gastric cancer and cachexia receiving chemotherapy (1st-3rd line) were randomized (1:1) to receive oral anamorelin 100 mg daily for 12 weeks (Group A) or no anamorelin (Group N). Randomization was conducted using a computer-generated sequence, stratified be participating institution and the type of surgical procedure. The primary endpoint was the change in lean body mass (LBM) at 8 weeks. The primary, secondary, and safety analyses were performed in the modified per-protocol population, which included all patients who received at least one dose of the assigned treatment and did not meet major protocol violations. This study is registered with the Japan Registry of Clinical Trials, jRCTs051210108. Findings: Between November 17, 2021 and July 4, 2024, a total of 217 patients were recruited. Of these, 14 patients did not meet the eligibility criteria, and 203 patients were subsequently randomised. Ultimately 101 in Group A and 97 in Group N were included in the final analysis. At 8 weeks, the increase in mean LBM was greater in Group A (+0.99 kg; 95% CI +0.34 to +1.64) compared to Group N (+0.14 kg; -0.49 to +0.77), but the between-group difference did not reach statistical significance (P = 0.063). As adverse events potentially related to anamorelin, hyperglycemia was observed in Group A: Grade 1-2 in 4 patients (4%) and Grade 3 in 1 patient (1%). No cases of hyperglycemia were observed in Group N. There were no treatment-related deaths in either group. Interpretation: Although no significant difference was observed between the two groups in the primary endpoint, anamorelin showed a trend toward increased LBM with good tolerability, suggesting potential benefit in gastric cancer cachexia. The randomized multicenter design strengthens the findings, though small sample size and treatment heterogeneity are limitations. These results support further evaluation of anamorelin to improve physical condition in this population with limited treatment options. Funding: Ono Pharmaceutical Co., Ltd.