The impact of excess weight and body fat on clinical outcomes of immune checkpoint inhibitors according to gender

The impact of body-mass index (BMI) on immune checkpoint inhibitor efficacy and toxicity has not been clearly characterized. We analyzed the association between BMI, and body fat (%BF), with the efficacy and toxicity of ICIs across three solid tumors in a real-life setting. Melanoma, lung and urothelial cancer patients treated with ICIs at our institution were included. BMI (kg/m2) and %BF (CUN-BAE) were calculated retrospectively. We studied the association between BMI/%BF and objetive-response-rate (ORR), progression-free survival (PFS), overall survival (OS) and immune-related adverse events (irAEs). Among the 356 patients included, 177 (49.7%) had a BMI ≥ 25 kg/m2. Mean BMI was 25.3 ± 4.2 kg/m2, and %BF 30.5 ± 6.3%. ORR was achieved in 155 patients (46.8%). Median PFS and OS was 4 and 11 months, respectively. There were no differences in ORR across BMI categories. In contrast, normal %BF was associated with better ORR in men (81.8% vs. 41.7%, p = 0.024), but not in women (p = 0.074). Additionally, no association was observed between BMI/%BF and irAEs (p = 0.762). Notably, those developing any-grade irAEs showed better ORR (p < 0.001), PFS (HR 1.6, p < 0.001) and OS (HR 1.7, p < 0.001), even adjusting by BMI/%BF, age, gender, primary tumor or ICI regimen. Our results suggest that in patients with advanced cancers treated with ICIs, BMI was not correlated with clinical outcomes or survival. However, men with normal %BF showed better ORR compared to men with excess-%BF, but this pattern was not observed in women. These findings support to consider gender and body composition as stratification factors in trials.