Real-world Analysis of Urinary Protein-to-Creatinine Ratio and Blood Pressure in Lenvatinib Therapy

Background/Aim: Lenvatinib is widely used to treat several malignancies. Proteinuria is a frequent adverse event associated with lenvatinib; however, limited evidence exists regarding risk factors for severe proteinuria–specifically, a urine protein-to-creatinine ratio (UPCR) ≥3.5 g/g creatinine (g/gCre)–across multiple cancer types. This study aimed to identify risk factors for UPCR ≥3.5 g/gCre in patients with thyroid cancer, hepatocellular carcinoma, and endometrial cancer treated with lenvatinib. Patients and Methods: This retrospective study examined the incidence and risk factors for UPCR ≥3.5 g/gCre in patients treated with lenvatinib between January 2018 and December 2022. Of 195 patients screened, 131 met the inclusion criteria (thyroid cancer: 55; hepatocellular carcinoma: 55; endometrial cancer: 21). Ethics approval was obtained from the institutional review board. Results: UPCR ≥3.5 g/gCre occurred in 34 patients (26.0%), with the highest rate in patients with thyroid cancer (45.5%). Univariate Cox proportional hazards analysis identified an initial lenvatinib dose of ≥20 mg/day [hazard ratio (HR)=2.54; 95% confidence interval (CI)=1.10-5.89; p=0.030] and the onset of grade 3 hypertension after treatment initiation (HR=2.65; 95% CI=1.10-6.40; p=0.031) as significant risk factors. Multivariate analysis also confirmed these factors as independent predictors: initial lenvatinib dose ≥20 mg/day (HR=2.62; 95% CI=1.12-6.14; p=0.027) and grade 3 hypertension after treatment initiation (HR=2.70; 95% CI=1.11-6.57; p=0.029). Conclusion: These findings emphasize the need for intensive blood pressure management and regular UPCR monitoring during lenvatinib therapy to reduce the risk of severe proteinuria, regardless of cancer type.