Association of baseline serum albumin with treatment-related toxicities in patients receiving tyrosine kinase inhibitors: a real-world cohort study

Background Tyrosine kinase inhibitors (TKIs) are widely used across multiple malignancies, but treatment-related toxicities remain a major cause of healthcare utilization and treatment modification. Serum albumin is a routinely available biomarker that reflects nutritional status, systemic inflammation, and physiologic vulnerability and may also influence the pharmacokinetics of highly protein-bound agents. Real-world data evaluating the association between baseline albumin levels and TKI-related toxicity are limited. Methods We conducted a retrospective cohort study of adult cancer patients treated with TKIs at a tertiary oncology center. Patients were stratified by baseline serum albumin (< 3.5 vs. ≥ 3.5 g/dL). The primary outcome was time to first documented treatment-related toxicity. Secondary outcomes included any documented toxicity, hospitalization or emergency department (ED) visit following toxicity, treatment modification due to toxicity, and overall survival. Kaplan–Meier analyses and Cox proportional hazards models were used to evaluate time-to-event outcomes, adjusting for clinically relevant covariates. Results A total of 369 patients were included, of whom 121 (32.8%) had baseline hypoalbuminemia. Patients with hypoalbuminemia had poorer performance status and greater metastatic burden at baseline. The overall incidence of documented toxicity was similar between groups (61.2% vs. 61.7%; p = 0.921). However, hospitalization or emergency department attendance following toxicity was more frequent in patients with hypoalbuminemia (28.9% vs. 17.7%; p = 0.014). In unadjusted analysis, time to first toxicity was shorter in the hypoalbuminemia group. This association was attenuated after adjustment for age, sex, ECOG performance status, metastatic burden, liver disease, and TKI class (adjusted HR 0.93, 95% CI 0.69–1.24; p = 0.605). Conclusions Baseline hypoalbuminemia was associated with shorter unadjusted time to first toxicity and greater toxicity-related healthcare utilization despite a similar overall incidence of toxicity. The time-to-toxicity association was attenuated after multivariable adjustment, suggesting that low albumin may primarily reflect underlying clinical vulnerability rather than independently predict TKI-related toxicity.