Efficacy and Safety of Pharmacotherapy in Cancer-Related Anorexia and Cachexia Symptoms: An Updated Systematic Review and Network Meta-Analysis

Introduction: Cancer-associated cachexia syndrome (CACS) is a complex condition characterized by anorexia, weight loss, and muscle wasting, significantly affecting quality of life and treatment outcomes. The comparative efficacy and safety of pharmacological treatments remain uncertain. Methods: A systematic review and network meta-analysis were conducted using randomized clinical trials (RCTs). Three databases were searched for studies published between 2000 and 2024. The analyzed outcomes included absolute weight gain, improvement in the anorexia-cachexia subscore (ACS), and the risk of serious adverse events (AEs). Results: Nine studies involving 1,505 participants were analyzed. Olanzapine demonstrated the most significant weight gain (MD 4.6 kg, 95% CI: 0.82–8.38), while ponsegromab 400 mg and anamorelin 100 mg were effective in maintaining weight, with gains of 3.26 kg (95% CI: 2.35–4.17) and 2.38 kg (95% CI: 1.82–2.94), respectively. However, the network meta-analysis did not confirm the superiority of olanzapine over ponsegromab or anamorelin. Mirtazapine showed limited benefits in weight gain. Regarding ACS, olanzapine demonstrated the highest efficacy, with significant improvement compared to ponsegromab 400 mg (MD 6.5, 95% CI: 1.3–11.7), anamorelin 100 mg (MD 6.9, 95% CI: 1.6–12.1), mirtazapine 15 mg (MD 10.0, 95% CI: 5.8–14.2), ponsegromab 200 mg (MD 10.3, 95% CI: 6.1–14.5), and anamorelin 50 mg (MD 10.3, 95% CI: 5.1–15.4), confirming its superior ACS improvement through network meta-analysis. All but mirtazapine showed acceptable safety profiles, with serious AEs (odds ratio: 5.93, 95% CI: 2.35–14.96). Only mirtazapine showed an increased risk of serious AEs with an odds ratio of 5.93 (95% CI: 2.35–14.96). Conclusions: Olanzapine demonstrated notable benefits in weight gain and ACS improvement with a favorable safety profile while emerging agents like anamorelin and ponsegromab show promise in managing CACS.