Endocrine Abstracts

JOINT3428

Whether overweight/obesity has an impact on immune checkpoint inhibitor (ICIs) toxicity and efficacy is currently under debate. The present study was aimed at evaluating the occurrence of irAEs among cancer patients on ICI therapy according to baseline BMI and gender.

Patients and Methods: We performed a retrospective analysis of 130 patients (93 males and 37 females, male/female ratio 2.5:1; median age 67 years, range: 32-85) with different types of cancer treated with ICIs at a single center. The primary tumours were: non-small-cell lung carcinoma (n = 72, 55%), melanoma (n = 30, 23%), renal cell carcinoma (n = 17, 13%), and others (n = 3, 3%).

Results: At baseline evaluation, median BMI in the whole cohort was 22 (range 18,1-36,7), and median body weight 70,5 kg (range 47 – 117). According to WHO classification, 3 patients (2.3%) were defined as underweight, 83 patients (63,8%) as normal weight, 37 patients (28.5%) as overweight and 7 patients (5.41%) as obese. During follow-up, any irAEs occurred in 42 patients (32%; median age 69 years), with significant differences between sexes (28 males and 14 females, F to M ratio 2:1; P = 0.007). Among them, 41 (31.5% of the whole cohort) developed thyroid dysfunction (hypothyroidism and/or thyrotoxicosis) without difference by sex (P = 0.578), primary hypothyroidism being the most common irAEs (39 patients; 30% of the whole cohort). Twenty-nine patients developed also non-endocrine AEs [cutaneous (n = 10), gastro-intestinal (n = 9), pulmonary (n = 2) and rheumatic (n = 8)], and difference by sex was significant (P = 0.009). Development of AEs was associated with higher BMI: the prevalence of AEs was 59.5% in overweight/obese patients vs 40.5% in normal weight patients (P < 0.001). Patients who developed AEs had higher body weight (75,5 ± 12 kg vs 70.2 ± 11 kg, P = 0.017) and BMI (25 ± 3.5 kg/m² vs22.7 ± 3 kg/m², P = 0.002) than patients who did not, in both sexes. At uni- and multivariate regression analyses, BMI was confirmed as an independent predictor of risk for developing AEs (P < 0.001), with overweight/obese patients having a OR of 3.182 compared to normal weight/underweight patients. BMI ≥25 kg/m² and AEs occurrence were associated to a better ECOG performance status (P = 0.012, and P = 0.013, respectively), although no differences in PFS and OS emerged.

Conclusion: Occurrence of ICI-related toxicities was more frequent in overweight/obese patients compared to normal weight/underweight patients. A BMI ≥25 kg/m² was associated with increased risk for developing AEs in both sexes. No clear association between BMI and immunotherapy efficacy/prognosis was observed.