Survival and immunotoxicities in association with sex-specific body composition patterns of cancer patients undergoing immune-checkpoint inhibitor therapy-A systematic review and meta-analysis

Background: Imbalanced body composition is mechanistically connected to dysre-gulated immune activities. Whether overweight/obesity or sarcopenia has an impact on treat-ment results in cancer patients undergoing immune checkpoint inhibitor (ICI) therapy is currently under debate. We aimed to answer if survival rates and occurrence of immune -related adverse events (irAEs) were different in obese or sarcopenic patients.Methods: A systematic search was conducted in PubMed, Embase and CENTRAL for all re-cords published until July 2022 using specific search terms for body composition in combina-tion with terms for ICI regimens. Two authors screened independently. All studies that reported on body mass index or sarcopenia measures were selected for further analysis.Results: 48 studies reporting on overweight/obesity comprising of 19,767 patients, and 32 studies reporting on sarcopenia comprising of 3193 patients fulfilled the inclusion criteria. In the entire cohort, overweight/obesity was significantly associated with better progression- free survival (PFS; p = 0.009) and overall survival (OS; p <0.00001). Subgroup analyses strat-ified by sex revealed that overweight/obese males had the strongest survival benefit (PFS: p = 0.05; OS: p = 0.0005), and overweight/obese female patients did not show any. However, overweight/obese patients of both sexes had a higher risk to develop irAEs grade >3 (p = 0.0009). Sarcopenic patients showed significantly shorter PFS (p <0.0001) and OS (p <0.0001). The frequency of irAEs did not differ between sarcopenic and non-sarcopenic pa-tients.Conclusion: This meta-analysis suggests that body composition is associated in a sex-specific manner with survival and irAEs in cancer patients undergoing ICI treatment. 2023 Elsevier Ltd. All rights reserved.

Automated summary

This meta-analysis suggests that body composition is associated in a sex-specific manner with survival and immune-related adverse events (irAEs) in cancer patients undergoing immune checkpoint inhibitor (ICI) therapy. Overweight/obesity is significantly associated with better progression-free survival (PFS) and overall survival (OS), but a higher risk of developing irAEs grade >3. Sarcopenic patients have significantly shorter PFS and OS, but the frequency of irAEs does not differ.