YI YIN ^1* Fengli Sun ^2* Youpeng Jin ^1*

• ¹ Shandong Provincial Hospital, Jinan, China
• ² The Second Hospital of Shandong University, Jinan, Shandong Province, China

Background: Pralsetinib, a selective oral inhibitor of rearranged during transfection (RET) fusion proteins and oncogenic RET mutants, has shown significant efficacy in treating RET fusion-positive non-small cell lung cancer and thyroid cancer. However, since pralsetinib was approved in the United States in September 2020, there were limited reports of post-marketing adverse events (AEs). In this study, we aimed to analyze the AEs signals with pralsetinib on the basis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to provide instructions in clinical practice. Methods: All AE reports were obtained from the FAERS database from the first quarter (Q3) of 2020 to the second quarter (Q2) of 2024. Various signal quantification techniques were used for analysis, including reporting odds ratios, proportional reporting ratios, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker (MGPS)-based empirical Bayesian geometric mean. Results: Out of 8,341,673 case reports in the FAERS database, 1,064 reports of pralsetinib as the 'primary suspected (PS)' AEs were recorded, covering 26 system organ classes and 256 preferred terms. 62.5% of reports were from consumers rather than healthcare professionals. The most common systems were general disorders and administration site conditions (n=704), investigations (n=516) and gastrointestinal disorders (n=405). A total of 95 significant disproportionality PTs conforming to the four algorithms simultaneously. AEs that ranked top three at the preferred terms (PTs) level were hypertension (n=80) ,asthenia (n=79) and anaemia (n=65). Of the 95 PTs with significant disproportionation, unexpected significant AEs such as blood calcitonin increased，myocardial necrosis marker increased and cystitis bacterial were observed which were not mentioned in the drug's instructions. The median onset time of pralsetinib-associated AEs was 41 days (interquartile range [IQR] 14-86 days). The majority of the AEs occurred in 30 days (42.86%). Conclusion: Our pharmacovigilance analysis of real-world data from the FEARS database revealed the safety signals and potential risks of pralsetinib usage. These results can provide valuable evidence for further clinical application of pralsetinib and are important in enhancing clinical medication safety.