Selinexor dose optimization: A retrospective analysis.

296 Background: Several oral oncolytics are approved at doses that require early and frequent intervention to manage associated toxicities. This retrospective analysis investigated efficacy and safety outcomes of patients initiated on lower doses (≤ 80 mg) of selinexor compared to those who started at higher doses (> 80 mg). Methods: All patients who were prescribed selinexor between December 18, 2020 and November 1, 2023 were included. Patients were categorized based on initial doses that were less than or equal to 80 mg or more than 80 mg. This cutoff was determined based on guidance released by Texas Oncology’s Pharmacy and Therapeutics (P&T) committee recommending that selinexor be initiated at doses not to exceed 80 mg per week. The primary endpoint was progression-free survival (PFS), defined as the time from initiation of selinexor to disease progression per physician assessment or death. Secondary endpoints included differences in rates of dose interruption, reduction, and discontinuation. Total cost of care and waste related to therapy was also assessed. PFS data was analyzed using a log-rank test. A total of 28 patients were reviewed, 7 in the > 80 mg group and 21 in the ≤ 80 mg arm. Results: Patients starting on lower doses of selinexor required fewer dose interruptions (29% vs 71%) and reductions (29% vs 57%), had lower rates of discontinuation due to adverse events (0% vs 50%), and less waste ($1,095.36 vs $13,418.13 average waste per patient) compared to those who were initiated on doses that exceeded 80 mg. The lower dosing did not result in a statistically significant difference in median PFS (119 days vs 80 days; p = 0.588). Conclusions: Real-world data may differ substantially from clinical trial findings, and this study highlights the importance of identifying optimal doses for oral oncolytics based on real-world experience. This data suggests that lower initial dosing may improve selinexor’s safety profile without compromising efficacy.