Prognostic factors and treatment outcomes in stage IV endometrial carcinoma: A 13-year single center experience.

e17630 Background: Systemic therapy is the cornerstone of managing stage IV endometrial cancer (EC). Treatment has expanded beyond platinum-taxane chemotherapy to targeted agents (e.g., bevacizumab) and immunotherapy. Multimodal therapy may improve outcomes, but real-world data remain limited. We aim to evaluate clinical outcomes and predictors of overall survival (OS) and progression-free survival (PFS) in stage IV EC. Methods: We retrospectively analyzed stage IV EC patients treated at Cleveland Clinic (1/2010–12/2022). Demographics, ECOG status, treatments, and outcomes were recorded. Treatment response was assessed using RECIST 1.1. OS and PFS were estimated using Kaplan-Meier, and associations were evaluated via Cox proportional hazards regression. Results: Among 157 patients, median age was 65 years (IQR: 60–72), 77% (n=121) were White, and 93% (n=146) had stage IVB. 41% (n=65) had endometrioid histology. Systemic therapy included Carboplatin + Paclitaxel/Docetaxel (38%) and Carboplatin + Paclitaxel/Docetaxel + Bevacizumab (31%). The overall response rate (ORR) was 56% (CR: 20%, PR: 36%). Median OS was 29 months (95% CI: 24–36), with a 5-year OS of 31%. Total abdominal hysterectomy with bilateral salpingo-oophorectomy +/-debulking significantly improved OS (HR 0.39, 95% CI: 0.25–0.61, p<0.001), while radiation did not (HR 1.03, 95% CI: 0.60–1.77, p>0.9). Stage IVA had better survival than IVB (HR 0.51, 95% CI: 0.21–1.27). Higher ECOG (≥2) was associated with a 4-fold increase in mortality risk (HR 3.94, 95% CI: 1.63–9.51, p=0.01). Bevacizumab did not improve OS (HR 1.07, 95% CI: 0.67–1.70, p=0.8). For second-line therapy, 42% (n=31) received chemotherapy, 27% (n=20) received Pembrolizumab ± Lenvatinib, and 30% (n=22) “other.” Pembrolizumab ± Lenvatinib did not significantly improve OS (HR 1.77, 95% CI: 0.90–3.47, p=0.10). Patients receiving "other" second-line treatments had significantly worse OS (HR 8.72, 95% CI: 3.71–20.5, p<0.001). Conclusions: Based on our real-word data, age, BMI and ECOG performance status were key prognostic factors in stage IV EC. Surgery improves OS. Patients receiving second-line therapy for recurrent EC have a poor prognosis. These findings highlight the need for more effective second-line therapies in stage IV EC. Multivariable Cox model for OS and PFS in stage IV EC. Characteristic HR (OS) HR (PFS) Age at diagnosis (years) 1.03 (1.01–1.05), p=0.005 1.02 (1.00–1.04), p=0.081 ECOG ≥2 3.94 (1.63–9.51), p=0.01 — BMI 1.02 (1.00–1.05), p=0.04 1.02 (1.00–1.04), p=0.12 Stage IVA vs. IVB 0.51 (0.21–1.27), p=0.012 0.46 (0.20–1.05), p=0.038 Surgery 0.39 (0.25–0.61), p<0.001 0.60 (0.40–0.91), p=0.015 Radiation 1.03 (0.60–1.77), p>0.9 1.89 (0.60–5.96), p=0.3 Systemic Therapy First 0.63 (0.37–1.06), p=0.076 1.03 (0.66–1.60), p>0.9 Second- Pembrolizumab ± Lenvatinib vs. Chemo 1.77 (0.90–3.47), p=0.10 — Second-line "Other" vs. Chemo 8.72 (3.71–20.5), p<0.001 —