Association of Omentectomy with Reduced Therapeutic Efficacy of Lenvatinib Plus Pembrolizumab in Patients with Endometrial Cancer.

e17613 Background: Recently, omentum has been suggested to be immunologically active. Therefore, we investigated the effect of prior omentectomy on the efficacy of lenvatinib + pembrolizumab (LP) therapy in patients with endometrial cancer (EC). Methods: This retrospective study included 95 patients with recurrent EC treated with LP between December 2021 and March 2025 at our institutions. The primary outcomes were progression-free survival (PFS) and overall survival (OS). Multivariable Cox regression analyses included factors such as omentectomy status, MMR status, FIGO stage (I/II or III/IV), histology (endometrioid or others), platinum-free interval (PFI) (<6 or ≥6 months) and the number of prior regimens (1 or ≥2). Results: Overall, 95 patients were enrolled in the study (omentectomy group, 50; no-omentectomy group, 45). Moreover, six patients in the no-omentectomy group, did not undergo primary surgery and predominantly presented with stage IV disease. Molecular profiling was used to identify 9 dMMR and 86 pMMR tumors. Advanced stage (III/IV), endometrioid histology, PFI <6 month, and ≥2 prior regimens were observed in 64%, 42%, 64%, and 30% of the patients in the omentectomy group and 58%, 60%, 60%, and 31% of the patients in the no-omentectomy group. Patients in the no-omentectomy had a significantly longer median PFS (15.4 vs. 8.2 months; p = 0.001) and OS (34.9 vs. 21.7 months; p = 0.090). Multivariable analysis revealed that omentectomy was independently associated with shorter PFS (HR 2.18; 95% CI, 1.23–3.88; p = 0.008), but was not an independent predictor of OS (HR 1.11; 95% CI 0.58–2.12; p = 0.750) [Table]. Histology-specific analyses of the major subtypes, including endometrioid carcinoma ( n = 48), serous carcinoma ( n = 20), and carcinosarcoma ( n = 18), revealed that omentectomy was associated with more favorable outcomes only in patients with serous carcinoma. Therefore, further analysis, excluding patients with serous carcinoma, was performed. In this non-serous cohort, multivariable Cox regression analyses demonstrated that omentectomy remained independently associated with shorter PFS (HR 3.29; 95% CI, 1.69–6.41; p < 0.001) and had a trend toward shorter OS (HR 1.99; 95% CI, 0.93–4.26; p = 0.076). Conclusions: Patients without prior omentectomy had better outcomes following LP therapy. Thus, omentum may contribute to antitumor immune regulation. Progression-free survival Overall survival Variables HR 95% CI p -value HR 95% CI p -value Omentectomy status OMTx vs No-OMTx 2.18 1.23–3.88 0.008 1.11 0.58–2.12 0.750 MMR status dMMR vs pMMR 0.36 0.13–1.00 0.051 0.19 0.04–0.87 0.032 FIGO stage III/IV vs I/II 1.00 0.58–1.75 0.992 1.48 0.74–2.98 0.272 Histology non-endometrioid vs endometrioid 1.09 0.63–1.88 0.768 2.47 1.22–5.00 0.012 PFI ≥6 vs <6 months 0.47 0.26–0.85 0.012 0.34 0.15–0.77 0.009 Number of prior regimens ≥2 vs 1 0.91 0.51–1.61 0.744 1.03 0.52–2.05 0.937