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 dysregulated immune activities. Whether overweight/obesity or sarcopenia has an impact on treatment 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 records published until July 2022 using specific search terms for body composition in combination 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 stratified 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 patients.

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.