Evaluation of the Relationship between Hypoalbuminemia and Oral Anticancer Drug-Related Adverse Events in Adults with Solid Tumor Malignancies

Presenter: Jessica Marini, PharmD, PGY2 Oncology Pharmacy Resident, Medical University of South Carolina

Co-Authors: Bailey Bass, Medical University of South Carolina College of Pharmacy; Jacob Rennebaum, Medical University of South Carolina College of Pharmacy; Erin Weeda, Medical University of South Carolina College of Pharmacy; Jagoda Misniakiewicz, Medical University of South Carolina; Amy Sion, Medical University of South Carolina

Background: Tyrosine kinase inhibitors (TKIs) have demonstrated efficacy in multiple solid tumors; however, more than 50% of patients receiving TKI therapy require dose modifications because of adverse events (AEs). TKIs are highly protein-bound drugs, and the presence of hypoalbuminemia may result in increased free-drug concentration, thereby leading to increased drug exposure and AEs.^1-8 Because hypoalbuminemia is common among patients with malignancy, we sought to define the relationship between TKI tolerability and low serum albumin levels in adults with solid malignant tumors.

Objective: To evaluate the relationship between hypoalbuminemia and TKI tolerability in adults with solid tumor malignancies.

Methods: This retrospective review included patients who received a highly protein-bound TKI, defined as >95% protein bound, between April 1, 2017, and March 31, 2020, for the management of solid tumors. Patients were excluded if they enrolled in clinical trials or received TKIs for hematologic malignancies. Chart review was conducted to collect baseline characteristics and data for analysis, including, but not limited to, age, weight, baseline albumin, type and stage of cancer at diagnosis, start date of TKI(s) therapy, AEs, albumin at each AE, any adjustments in therapy, date of treatment discontinuation and reason, if applicable. Hypoalbuminemia was defined as serum albumin <3.5 mg/dL.

Results: A total of 220 patients were included for analysis, with 101 patients having hypoalbuminemia at baseline. Patients with hypoalbuminemia had a worse performance status and a higher percentage of baseline liver disease and proteinuria versus patients without these conditions. There was a significantly higher all-cause discontinuation among patients with hypoalbuminemia than those without (83% vs 60%, respectively; P <.001). In addition, the rate of discontinuation because of intolerability was higher in patients with hypoalbuminemia (37% vs 16%, respectively; P <.001). The median time to treatment discontinuation was shorter in those with hypoalbuminemia (4 vs 21 months; P <.001). Hypoalbuminemia was associated with an increased rate of treatment discontinuation after adjusting for covariates (hazard ratio, 2.68; 95% confidence interval, 1.97-3.76). Of the patients who had at least 1 AE, 57% (98/171) had hypoalbuminemia at the time of the event.

Conclusion: Patients with hypoalbuminemia had a significantly higher incidence of AEs leading to earlier discontinuation of TKI therapy. A substantial number of patients who did have AEs had hypoalbuminemia at the time of the AE. Baseline hypoalbuminemia may be an important clinical assessment when initiating TKIs, but further studies are required to establish a relationship between lower starting doses and treatment outcomes.

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