Obesity exerts a wide arrange of physiological effects on health. Aside from its influences on oncogenesis, its impact on cancer outcomes is not completely understood. Adipose tissue is known to play a critical role in androgen and estrogen metabolism, and recent evidence established a link between male sex and T-cell exhaustion, both of which may affect the responsiveness of the immune system to immunotherapy. Here, we explored the relationship between body mass index (BMI), sex, and overall survival in patients (pts) with metastatic cancers treated with immune checkpoint inhibitors (ICIs).
We retrospectively studied pts with metastatic cancers treated with first or second-line ICI between 2011-2017 at Ohio State University. Pre-treatment BMI was collected. Cox proportional hazards models were used to assess the association between variables. Effect modification by sex was assessed using an interaction term. Analyses were performed in SAS 9.4.
There was 688 pts included in our study. 403 (58.6%) were males and 285 (41.4%) were females. 286 (41.6%) had EOCG performance status 0, 283 (41.1%) had ECOG 1, 107 (15.5%) had ECOG ≥2, 12 (1.7%) had unknown ECOG. 360 (52.3%) received first-line ICI-based therapies and 328 (47.7%) received as second-line. The top 3 cancer types were: 277 (40.3%) melanoma, 157 (22.8%) non-small cell lung cancer, 67 (9.7%) renal cell carcinoma. Median BMI was 28.0 with interquartile range 23.9-32.4. For every unit increased in BMI, risk of death was decreased by 1.8% (HR=0.982 with 95% CI 0.969-0.995, p=0.007) in the overall cohort. However, the associations of BMI with death were different in male VS female (interaction p= 0.003). In male pts, for 1 unit increased in BMI, the hazard of death decreased by 3.6 % (HR=0.964 with 95 % CI 0.946 - 0.982, p<0.001); Among female pts, there was reversed but not significant association (HR=1.003 with 95% CI 0.985-1.022, p=0.726). In multivariate analysis, BMI was a significant prognostic factor for survival after adjusting for ECOG, line of therapy, and cancer types in male pts only.
High BMI in male, but not female, was associated with improved overall survival in pts with metastatic cancers treated with ICIs.
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All authors have declared no conflicts of interest.