Association of steroid exposure with overall survival and hypersensitivity reaction risk in paclitaxel-treated patients with gynecologic cancers.

5541 Background: Paclitaxel remains a first-line agent in chemotherapy regimens for gynecologic cancers but is associated with hypersensitivity reactions (HSRs) in up to 40% of patients. Though this risk is largely mitigated by dexamethasone-based premedications, preclinical studies suggest that dexamethasone can induce treatment resistance through enhanced DNA repair capacity, immune suppression, or inhibition of apoptosis, raising concern that pretreatment could compromise paclitaxel efficacy. Furthermore, the effect of cumulative steroid exposure on survival outcomes remains unknown. This study evaluates the impact of cumulative steroid exposure on overall survival (OS) and explores factors associated with HSRs among paclitaxel-treated patients with gynecologic cancers. Methods: This IRB-approved retrospective cohort study included patients with gynecologic malignancies treated with paclitaxel-based chemotherapy at the R.J. Zuckerberg Cancer Center, Northwell Health Cancer Institute, New York, between May 2023 and December 2024. Treatment characteristics and outcomes data were analyzed using univariable and multivariable zero-inflated Poisson regression models for HSRs and Cox regression models for OS. Results: A total of 163 patients who completed at least three cycles of paclitaxel-based chemotherapy were included. The median age (range, 38-87) was 66 years. Patients were 49% White, 18% Asian, 17% Black, 6% Hispanic, and 11% other or unknown. Cancer types included endometrial cancer (53%), ovarian/peritoneal (42%), cervical (4%), and vaginal (1%). At initial diagnosis, 30% of patients had AJCC stage I disease, 31% stage II-III, 9% stage IV, and 30% had insufficient staging data. Most patients (85%) were newly diagnosed. Twenty one percent of patients developed at least one HSR. Body surface area, race, and prior exposure to paclitaxel were not independently associated with HSRs. In contrast, stage IV disease at diagnosis was associated with a higher rate of HSR compared with stage I disease, with a rate ratio of 2.83 (95% CI 1.01-7.93; p=0.048) after adjustment for key confounders. Cumulative dexamethasone exposure did not impact OS in either univariable or multivariable analyses. Conclusions: HSRs occurred in 21% of paclitaxel-treated patients and were independently more common among those with stage IV disease. This suggests that greater disease burden may reflect differences in immune responsiveness that predispose to HSRs. While dexamethasone is commonly used to improve treatment tolerability and reduce the risk of HSRs, cumulative exposure did not impact OS. Further studies are needed to clarify the mechanisms underlying paclitaxel-associated HSR and to define the optimal role of steroid premedication.