Tolerability Assessment of Tyrosine Kinase Inhibitors in Patients with Solid Tumor Malignancies and Hypoalbuminemia

Abstract

Abstract Background: Hypoalbuminemia is common in patients with advanced solid tumor malignancies, where there is an increased unbound fraction of highly protein-bound drugs, potentially leading to higher free drug concentration exposure and more toxicities. Despite the increased use of highly protein-bound tyrosine kinase inhibitors (TKIs) in cancer treatments over the decades, the tolerability of these agents in patients with hypoalbuminemia is not fully known. Our aim is to assess whether patients on oral TKIs with hypoalbuminemia are at higher risk for experiencing medication-related adverse events, therefore requiring careful considerations. Materials and Methods: This is a single-center, retrospective study including patients ≥ 18 years of age with a solid tumor malignancy who had taken at least one dose of oral TKIs with a protein binding of ≥ 90% between 06/01/2016 and 06/01/2021. Results: Patients with hypoalbuminemia had shorter time on treatment (median Kaplan-Meier (KM) estimate: 2.8 months (95 % CI 2.3–4.5 months) vs. 4.3 months (95 % CI 2.8 –6.4 months), p=0.003) compared to those without hypoalbuminemia. In patients who had TKI discontinuation, dose reduction was associated with longer time on treatment in patients in the normal albumin group compared to patients in the hypoalbuminemia group or patients without dose reduction (p<0.0001). Patients in the hypoalbuminemia group experienced significantly more grade 3/4 adverse events compared to those in the normal albumin group (73% vs. 27%, p<0.0001). Conclusion: Hypoalbuminemia is a risk factor for shorter time on treatment in patients with solid tumor malignancies, when taking highly protein-bound oral TKIs.