Prognostic Value of the Systemic Immune-Inflammation Index in Advanced Endometrial Cancer Treated with Pembrolizumab–Lenvatinib: A Retrospective Real-World Study

Background: The prognostic role of the Systemic Immune-Inflammation Index (SII) in patients with endometrial cancer (EC) treated with pembrolizumab plus lenvatinib (Len-Pem) is unknown. In this study, the association between baseline SII and progression-free survival (PFS) was evaluated. Methods: This is a monocentric, observational, retrospective/ambispective study including patients with advanced, recurrent, or metastatic mismatch repair proficient (pMMR) EC treated with Len-Pem. Results: Fifty-three patients were enrolled, with a median age of 64 years. Median PFS in the overall population was 7.1 months; median OS was 15 months. Patients with baseline SII ≤ 540 had significantly longer PFS (12.5 months) compared to those with SII > 540 (5.5 months; HR 2.94, p = 0.004). Higher SII was also significantly associated with increased risk of specific toxicities, including nausea, anorexia, and vomiting. The Overall Response Rate (ORR) was 42%, and Disease Control Rate (DCR) was 71%. Conclusion: Our real-world study supports the hypothesis-generation of a prognostic role for SII in predicting outcomes and toxicity in EC patients treated with Len-Pem. SII may serve as a cost-effective, accessible biomarker to stratify patients and hypothetically guide clinical decision-making. Further prospective studies are warranted to validate its clinical utility and to optimize dosing strategies that balance efficacy and tolerability.