Factors Associated with Hypophosphatemia Among Patients with Malignancy on Antineoplastic Agents

Background: Hypophosphatemia is an important electrolyte disturbance leading to muscle weakness and osteomalacia. Patients with malignancy are prone to hypophosphatemia due to malnutrition and antineoplastic agents-induced tubular injury. However, serum phosphate is not routinely measured, and hypophosphatemia is often overlooked. The study aims to investigate risk factors for hypophosphatemia during the treatment of malignancy. Methods: This is a retrospective cohort study on patients with malignancy on anti-neoplastic agents from 2018 to 2023. Antineoplastic agents (used more than 500 times) associated with hypophosphatemia (defined as phosphate levels <2.0 mg/dL) were examined by multi-level mixed-effects logistic regression analyses. The data were adjusted for age, sex, serum albumin, eGFR, types of malignancy, and other medications which potentially affect electrolytes. Results: Out of 11475 patients, 4743 had measurements of phosphate at least once. Mean age was 67.7 (13.2) years, 65.8% were male, and the mean eGFR was 70.8 (41.0) mL/min/1.73m2. The incidence of hypophosphatemia was 3.16 events/100 patient-measurements. Antineoplastic agents associated with hypophosphatemia are shown in Table. Of note, two immune-checkpoint inhibitors (durvalumab and nivolumab) were included, which suggests class effects. Other than anti-neoplastic agents, higher age, higher eGFR, and lower albumin levels were associated with the development of hypophosphatemia. Conclusion: Panitumumab, fludarabine, durvalumab, nivolumab, cyclophosphamide, and etoposide were associated with hypophosphatemia. Although the results might be affected by practice patterns of our facility, phosphate levels should be monitored when these agents are prescribed, especially to elderly patients with hypoalbuminemia. Funding: Government Support – Non-U.S. Anti-neoplastic agents associated with hypophosphatemia - OR (95% CI) Panitumumab 4.30 (1.54-12.02) Fludarabine 3.66 (2.61-5.14) Durvalumab 2.58 (0.99-6.72) Nivolumab 2.29 (1.30-4.05) Cyclophosphamide 2.07 (1.56-2.75) Etoposide 1.57 (1.11-2.22)