Characterizing platinum resistance in recurrent endometrial cancer: A retrospective cohort study.

e17620 Background: Endometrial cancer is the most diagnosed gynecologic malignancy in Western countries, with a lifetime risk of approximately 2.5% in the United States. Twenty-nine percent of patients present with advanced-stage disease. The risk of recurrence is 37.5% in stage III disease and 66.7% in stage IV. Median survival in the recurrent setting is less than two years. Platinum resistance is defined in ovarian cancer as recurrence or progression of disease within 6 months of receipt of platinum-based chemotherapy. There lacks consensus on how to define platinum resistance in EC. The aim of this study was to assess outcomes of patients who received platinum-based therapy for first recurrence in EC after up-front treatment with platinum, compared to those who received a non-platinum-based second line treatment, with the goal of describing platinum-free interval in EC. Methods: A retrospective chart review was conducted that included patients treated for recurrent EC at a single institution from 2009-2024. Patients who received platinum with initial treatment were included. One cohort of patients were treated for recurrence with a platinum-based regimen while a second cohort received non-platinum-based therapy. Kaplan-Meier method was used to assess progression free survival (PFS). A cox regression model was performed comparing PFS between the two groups, adjusting for age at diagnosis, race, stage, histology, molecular profile, location of recurrence, number of cycles of treatment for first recurrence, primary treatment, and time to first recurrence. A p-value less than 0.05 was considered significant. Results: A total of 99 patients were included. Twenty-five percent of patients received platinum-based second line therapy while 75% received non-platinum therapy. A majority of patients had non-endometrioid histology (72%), advanced-stage disease at diagnosis (82%), and experienced distant recurrence (66%). Median PFS after first recurrence was 57 months (95% CI 20-262 months) in the platinum group compared to 22 months (95% CI 19-27 months) in the non-platinum group (p = 0.02). Median time to first recurrence was significantly different between the two groups, 11.0 months (IQR 5.1-15.4 months) in the platinum group versus 3.32 months (IQR 0.6-8.1 months) in the non-platinum group (p = 0.002). After adjusting for covariates mentioned above, patients who received non-platinum second line treatment had a 3.69 times higher risk of disease progression than those who received platinum treatment again (HR 3.69; 95%CI 1.53-8.85, p = 0.0035). Conclusions: Our study suggests a benefit to rechallenge with platinum-based chemotherapy in first recurrence of EC in patients who have been previously exposed to platinum therapy. Further work is needed to determine the optimal platinum-free interval for retreatment with platinum in EC.