Asthenia in cancer patients receiving immune checkpoint Inhibitors (ICIs): the MOUSEION-11 systematic review and meta-analysis

Introduction: The MOUSEION-11 systematic review and meta-analysis aimed to assess the rates of asthenia in patients receiving immune checkpoint inhibitors (ICIs) compared with those who received non-immunotherapeutic regimens or placebo ones. Methods: The MOUSEION-11 was recorded with PROSPERO n. CRD420250654013 and carried out following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Results: For any-grade asthenia, 39 studies were included. The pooled prevalence was 15.6% (95% CI: [10.4%; 22.7%]) under a random-effects model, with significant very high heterogeneity (P < 0.001; tau2 = 2.15; I2 = 93.5%. No evidence of publication bias was detected (Egger's test P = 0.538). For grade ≥ 3 asthenia, 36 studies showed a pooled prevalence of 1.5% (95% CI: [0.6%; 3.4%]), with very high heterogeneity (I2 = 85.1%, P < 0.001) and evidence of publication bias (Egger's test P < 0.001). In comparative analyses, 14 studies demonstrated that immunotherapy was associated with significantly higher odds of any-grade asthenia compared with placebo (OR = 7.18; 95% CI: [3.82; 13.49]; P < 0.001; I2 = 63.3%), without significant publication bias (P = 0.077). Conversely, in 15 studies, immunotherapy was associated with significantly lower odds of grade ≥ 3 asthenia compared with placebo (OR = 0.06; 95% CI: [0.04; 0.09]; P < 0.001; I2 = 20.8%), with no evidence of funnel plot asymmetry (Egger's test P = 0.084). Conclusion: Despite the incidence of asthenia in patients receiving ICI, no treatments have been tested to palliate ICIs-induced asthenia.