A randomized controlled trial evaluating anamorelin hydrochloride in patients with gastric cancer cachexia (TEAM-GUSTO).

e16037 Background: Cancer cachexia is a multifactorial metabolic syndrome associated with treatment interruption, deterioration in quality of life (QOL), and poor outcomes in patients with advanced cancer. Anamorelin, a ghrelin receptor agonist, has demonstrated efficacy in improving appetite, lean body mass (LBM), and body weight in lung cancer cachexia (ROMANA-1/2); however, randomized evidence in gastrointestinal cancers remains limited. We conducted a randomized controlled trial to evaluate the efficacy and safety of anamorelin in patients with gastric cancer cachexia. Methods: This multicenter, open-label randomized controlled trial was conducted across 10 institutions. Patients with unresectable or recurrent gastric cancer and cachexia receiving or planned for 1st–3rd line chemotherapy were randomized 1:1 to oral anamorelin hydrochloride 100 mg once daily for 12 weeks (Group A) or no anamorelin (Group N). Randomization was stratified by institution and gastrectomy status. The primary endpoint was change in lean body mass (LBM) at week 8. Secondary endpoints included total weight, quality of life (QOL), tumor response, chemotherapy compliance, and safety. Prespecified subgroup analyses included performance status, line of chemotherapy, and baseline plasma ghrelin categorized by the median value. The trial was registered with the Japan Registry of Clinical Trials (jRCTs051210108). Results: Between October 2021 and July 2024, 203 patients were randomized; 198 were evaluable (Group A 101; Group N 97), with balanced baseline characteristics. At week 8, mean LBM change was +0.99 kg (95% CI 0.34–1.64) in Group A and +0.14 kg (–0.49–0.77) in Group N (P = 0.063). In a prespecified analysis of covariance adjusting for baseline LBM and type of gastrectomy, the adjusted mean difference in LBM change was +1.077 kg (95% CI 0.184–1.969; P = 0.018). Total weight increased in Group A (+1.17 kg; 95% CI 0.56–1.78) and decreased in Group N (–0.59 kg; –1.22–0.04) (P < 0.0001). Appetite-related QOL improved in Group A. No significant differences were observed in chemotherapy compliance or tumor response. Exploratory subgroup analyses suggested greater LBM benefit in patients with good performance status and those receiving first-line chemotherapy. Baseline ghrelin did not predict treatment effect. No severe treatment-related adverse events occurred. These findings indicate that anamorelin can be administered during chemotherapy without compromising treatment delivery, supporting its oncologic feasibility as a supportive intervention. Conclusions: In gastric cancer cachexia, anamorelin did not achieve a statistically significant increase in LBM at 8 weeks but significantly improved body weight and appetite-related QOL with a favorable safety profile. Anamorelin represents a feasible supportive option during chemotherapy in multimodal gastric cancer care. Clinical trial information: jRCTs051210108.