Safety profile of isocitrate dehydrogenase inhibitors in cancer therapy: a pharmacovigilance study of the FDA Adverse Event Reporting System.

Background: Isocitrate dehydrogenase (IDH) inhibitors hold promise for IDH-mutated cancer patients and demonstrated favorable clinical efficacy. Nonetheless, a comprehensive understanding of the associated toxicities of IDH inhibitors remains notably lacking.

Research design and methods: This pharmacovigilance analysis utilized the FDA Adverse Event Reporting System (FAERS) database to assess notable adverse events (AEs) attributed to IDH inhibitors (enasidenib and ivosidenib) from January 2018 to December 2023.

Results: In the FAERS database, 2,905 enasidenib-associated and 1,289 ivosidenib-related AEs records were identified, respectively. The toxicity profiles of IDH1 and IDH2 inhibitors exhibited notable similarities. The most commonly significant system-organ classes induced by IDH inhibitors encompassed general disorders and administration site conditions, investigations, gastrointestinal disorders, and infections and infestations. The most common AEs included nausea, fatigue, diarrhea, decreased appetite, decreased platelet count, fever, pneumonia, weakness, sepsis, constipation, vomiting, rash, and reduced hemoglobin levels. Notably, temporal analysis of AEs shows enasidenib and ivosidenib have median onset times of 137 and 75 days, with distinct initial peak frequencies.

Conclusion: The reversible nature of the toxicities associated with IDH inhibitors underscores their promise as a therapeutic agent with a favorable safety profile.