Association Between Body Mass Index and Treatment Toxicity in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib or Pazopanib.

Background/Objectives: Sunitinib and pazopanib are administered at fixed doses in patients with metastatic renal cell carcinoma (mRCC), without adjustment for body composition. This study aimed to investigate the association between body mass index (BMI) and treatment-related toxicity and treatment discontinuation in patients with mRCC receiving first-line sunitinib or pazopanib. Methods: A total of 136 patients with mRCC treated with sunitinib (n = 90) or pazopanib (n = 46) were retrospectively evaluated. BMI was compared according to toxicity grade (1-2 and 3-4) and treatment discontinuation using Student's t-tests and chi-square/Fisher's exact tests. Given the limited number of grade 3-4 toxicity events, Firth's penalized logistic regression was used for multivariable analysis, with adjustment for age, sex, and treatment type. BMI was evaluated as a continuous variable in the primary model and categorically in a supportive analysis. p < 0.05 was considered statistically significant. Results: Higher BMI was significantly associated with grade 1-2 (p < 0.001) and grade 3-4 toxicity (p < 0.001). In the Firth penalized multivariable analysis, higher BMI remained independently associated with grade 3-4 toxicity (OR per 1 kg/m2 increase, 1.160; 95% CI, 1.057-1.283; p = 0.0015). Increasing age (OR per 1-year increase, 1.061; 95% CI, 1.021-1.106; p = 0.0022) and sunitinib treatment (OR, 2.629; 95% CI, 1.104-6.785; p = 0.028) were also independently associated with grade 3-4 toxicity. In the supportive categorical analysis, obesity (BMI ≥ 30 kg/m2) was associated with higher odds of grade 3-4 toxicity compared with BMI < 25 kg/m2 (OR, 4.173; 95% CI, 1.533-11.982; p = 0.005). Conclusions: A higher BMI was associated with a greater likelihood of grade 3-4 TKI-related toxicity in patients with mRCC receiving fixed-dose sunitinib or pazopanib. BMI may represent a practical clinical marker for identifying patients who warrant closer toxicity monitoring.