Tucker, Calvin E.

e24165 Background: Taxanes are associated with a higher incidence of immediate hypersensitivity reactions (HSRs) compared to other classes of chemotherapeutic agents, even with adequate premedication. This study evaluates whether a titrated infusion protocol reduces the rate of first-dose HSRs to taxanes. Methods: This was a retrospective cohort study conducted at a single site hematology/oncology infusion center. The fixed-rate arm consisted of patients from January 2022 to July 2023 who received a fixed infusion rate for their first dose. The titration arm comprised patients from August 2023 to July 2024 who underwent a three-step titration protocol for their first dose. The primary endpoint was the rate of immediate HSRs during the first lifetime dose of docetaxel or paclitaxel. Secondary endpoints included HSR severity, HSRs during the first or second dose, and rate of treatment discontinuation due to HSRs. Results: Of 479 patients included (240 fixed-rate; 239 titration), HSRs occurred in 7.1% of the fixed-rate group and 11.3% of the titration group (OR 1.67, 95% CI 0.89-3.15; p= 0.1104). There were no differences in the severity of HSRs or in the rate of treatment discontinuation among both groups. Conclusions: The use of a titrated infusion protocol for first lifetime dose taxanes did not significantly reduce the incidence or severity of immediate HSRs. These findings suggest that a titration protocol may not confer additional benefits over fixed-rate in this setting. Primary and secondary endpoints. Fixed (N=240) Titration (N=239) OR 95% CI p-value Primary Endpoint Rates of immediate HSR 17 (7.1%) 27 (11.3%) 1.67 0.89- 3.15 0.110 Secondary Endpoints Severity of immediate HSR N=17 N=27 Grade 1 10 (58.8%) 8 (30.8%) 0.637 Grade 2 6 (35.3%) 12 (46.2%) 0.157 Grade 3 1 (5.9%) 6 (23.1%) 0.059 Rates of immediate HSR with first or second dose combined N=471 infusions N=453 infusions 26 (5.5%) 37 (8.2%) 1.52 0.91-2.56 0.111 Taxane administration time (min) N=239 N=232 1-hour infusion 71.8 92.8 3-hour infusion 187.6 201.6 Rates of medication discontinuation due to immediate HSR N=26 N=37 1 (3.8%) 8 (21.6%) 6.90 0.81-59.17 0.069

PURPOSE Taxanes are associated with a higher incidence of immediate hypersensitivity reactions (HSRs) compared with other classes of chemotherapeutic agents, even with premedication. This study evaluates whether a titrated infusion protocol reduces the rate of first-dose HSRs to taxanes. METHODOLOGY This was a retrospective cohort study conducted at a single-site hematology/oncology infusion center. The fixed-rate arm consisted of patients treated from January 2022 to July 2023 who received a fixed infusion rate for their first dose. The titration arm comprised patients treated from August 2023 to July 2024 who underwent a three-step titration protocol for their first dose. The primary end point was the rate of immediate HSRs during the first lifetime dose of docetaxel or paclitaxel. Secondary end points included HSR severity, HSRs during the first or second dose, and rate of treatment discontinuation because of HSRs. RESULTS Of 479 patients included (240 fixed-rate; 239 titration), HSRs occurred in 7.1% of the fixed-rate group and 11.3% of the titration group (odds ratio, 1.67 [95% CI, 0.89 to 3.15]; P = .1104). There were no differences in the severity of HSRs or in the rate of treatment discontinuation among both groups. CONCLUSION The use of a titrated infusion protocol for first lifetime dose taxanes did not significantly reduce the incidence or severity of immediate HSRs. These findings suggest that a titration protocol may not confer additional benefits over fixed-rate in this setting.

8 Background: At Mayo Clinic, the implementation of an automated chemotherapy dose rounding program has resulted in significant cost savings when doses are rounded down to a vial size, however, the cost burden from drug waste continues to be a significant issue when rounding to a vial size is not within our 10% rounding allowance. The mismatch between drug doses and the marketed vial sizes, along with the limitations to the use of single dose vials is a recognized problem, resulting in billions of dollars of wasted drugs in the United States.The goal of our study was to quantify the cost of the wasted amount of chemotherapy and biologic drugs after the implementation of an automated dose rounding program. Methods: Using the electronic health record (EHR), data was collected for biologic and oncolytic agents administered from 1/1/2019 through 12/31/2021. Drugs with waste documented during preparation and that were administered to cancer patients were selected for analysis. The % of doses with waste documented was calculated based upon the total number of all doses given. The total cost of the drug administered along with the cost of the amount of drug wasted were calculated based upon costs listed in the EHR at the time of administration. Results: For the 3-year period, 446,832 doses were dispensed with 47,626 (10.7%) of those doses having waste documented. The total cost of the drugs with documented waste was $114,323,203 with 21.9% ($25,086,608) accounting sole for wasted drug. Five drugs accounted for 59% of the total cost of the drug waste (Table). When examining individual drugs with a high % of doses with documented waste, methoxsalen, epirubicin, eribulin, topotecan, & bortezomib each had > 70% of doses with a documented wasted amount. Conclusions: Despite having an aggressive institutional dose rounding policy, drug waste still results in considerable and significant costs to the Mayo Clinic System. Our data likely underestimates the total cost of drugs waste given that waste documentation requires manual entry into the EHR at the time of preparation. Our results support the need to create and develop solutions that could lead to reduced waste costs which include re-examining the weight based dosing of drugs, mandating pharmaceutical companies to have vial sizes that more appropriately meet the range of standard dosing, developing more multi-dose vials that can be shared across multiple patients, utilizing closed-system transfer devices to extend beyond-use-dating time, or requiring pharmaceutical companies to reimburse payers and patients for the cost of the amount wasted. Drug waste is still a considerable issue and one that needs to be addressed at a policy level.[Table: see text]