Being overweight or obese is an established risk factor for many malignancies and is associated with worse outcomes in several cancers. Although it is characterized by a metainflammatory state, little is understood about its impact in response to IO. Some studies in metastatic melanoma and renal cell carcinoma patients receiving IO demonstrated that being overweight or obese is associated with longer progression free survival (PFS) and overall survival (OS), and recently some studies have pointed towards a similar association in NSCLC. This study aimed to explore the impact of BMI in NSCLC patients treated with anti PD-1 IO.
This is a retrospective cohort study of NSCLC patients with advanced disease treated with pembrolizumab (≥1st line) or nivolumab (≥2nd line) in monotherapy. Patients were categorized into BMI<25 Kg/m2 and BMI≥25 Kg/m2 according to WHO definition.
114 patients were included, 70.2% male and 37.7% with BMI≥25 Kg/m2. Both groups were balanced in all characteristics except for less active smokers (p=0,034), more tumors with PD-L1 expression≥50% (p=0.025) and more dyslipidemic patients (p=0.047) in the BMI≥25 Kg/m2 group. Although in univariate analysis there was no association between BMI and PFS (HR=1.029; 95% CI 0.660-1.605; p=0.898) or OS (HR=1.012; 95% CI 0.638-1.607; p=0.959), in the multivariate model correcting for PD-L1 expression, hepatic and/or central nervous system metastasis, PS-ECOG and dyslipidemia, patients with BMI≥25 Kg/m2 had worse outcomes, both in PFS (HR=2.180; 95% CI 1.049-4.532; p=0.037) and OS (HR=2.364; 95% CI 1.062-5.263; p=0,035). Curiously, dyslipidemia was associated with better PFS in both univariate analysis (HR=0.572; 95% CI 0.355-0.920; p=0.021) and multivariate model (HR=0.421; 95% CI 0.206-0.859; p=0.017).
A BMI≥25 Kg/m2 was associated with shorter PFS and OS in our cohort. Our results differ from other studies, reinforcing the complex relationship between overweight, inflammation and IO response. The association found between dyslipidemia (not studied on previous studies) and PFS may suggest other factors play a role in this relationship and should be further investigated.
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All authors have declared no conflicts of interest.