Risk of tumor lysis syndrome associated with kinase inhibitors: Analysis of FAERS and real-world data.

Abstract

e24101 Background: Tumor lysis syndrome (TLS) is an oncological emergency caused by rapid tumor cell breakdown leading to the swift release of intracellular contents into the bloodstream overwhelming homeostatic mechanisms. This process can result in hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia and xanthine accumulation as a by-product of intracellular DNA release posing significant risks such as acute kidney injury, cardiac arrhythmias, seizures, multiorgan failure and rarely, death. While TLS can occur spontaneously it typically arises after the initiation of anti-cancer treatment especially in patients with a large tumor burden. In Q3 2024 FDA posted a Potential Signals of Serious Risks/New Safety Information Identified regarding TLS cases in Lenvatinib and Sorafenib users based on FDA Adverse Event Reporting System (FAERS) data. Methods: The current study presents a Disproportionality Analysis (DA) of FAERS data and explores Real-World Data (RWD) from TriNetX for the class of drugs known as Kinase Inhibitors (KIs) including Lenvatinib, Sorafenib, Sunitinib, Pazopanib, Axitinib and Cabozantinib. Results: DA using the FAERS dataset revealed above-threshold scores for TLS and these KIs (Table) indicating potential causal association between them. Analysis of RWD from TriNetX Global dataset (data cut-off 10 th Jan 2025) revealed a total of 380 TLS cases temporally related to these KIs (n= 95060). Among these therapies, Sorafenib showed the highest rate of TLS affecting 0.83% of patients (180 out of 21,700). In contrast Axitinib had the lowest incidence at 0.20% (20 out of 9,600 patients). The other therapies fell between these extremes with Lenvatinib, Pazopanib, Sunitinib and Cabozantinib showing TLS rates of 0.22%, 0.25%, 0.34% and 0.33% respectively. Conclusions: Analysis of FAERS and RWD revealed a considerable number of TLS cases post therapy with specified KIs indicating a need for inclusion of preventive measures including prophylaxis with hypouricemic agents, monitoring and early intervention for these therapies. The product labeling for this drug class may also require update to include relevant safety information, warnings and precautions. References: Tumor Lysis Syndrome in Patients With Solid Tumors: A Systematic Review of Reported Cases - PMC July - September 2024 | Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS) | FDA . Disproportionality analysis with FAERS data (Data cut-off 30 Sep 2024). KIs N EBGM (-) ROR (-) Lenvatinib 16 1.92* 3.79* Sorafenib 28 4.93* 9.02* Sunitinib 7 1.69* 3.15* Pazopanib 15 3.7* 6.28* Axitinib 12 0.62 1.08* Cabozantinib 6 0.9 1.8* *Indicates above-threshold on disproportionality statistical scores. EBGM (-): Empirical Bayes Geometric Mean - Lower Bound of 95% Confidence Interval. ROR (-): Reporting Odds Ratio - lower bound of the 95% confidence interval.