Prognostic value of Systemic Inflammation Index (SII) in advanced or recurrent endometrial cancer (EC) patients treated with pembrolizumab and lenvatinib: retrospective observational study experience

Background To evaluate the association between baseline Systemic Immune-Inflammation Index (SII) and progression-free survival (PFS) in patients with advanced, recurrent, or metastatic endometrial cancer (EC) treated with pembrolizumab plus lenvatinib (Len-Pem) in a real-world setting. Secondary objectives included assessment of SII in relation to overall survival (OS), adverse events (AEs), treatment discontinuations, dose modifications, and post-progression therapies. Methods This is a monocentric, observational, retrospective/ambispective study including 53 patients with advanced, recurrent, or metastatic mismatch repair proficient (pMMR) EC treated with pembrolizumab-lenvatinib (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%. The majority of patients (79%) required lenvatinib dose reductions. Adverse events of any grade were frequent, with fatigue (58%), hypertension (50%), and hypothyroidism (48%) being the most common. Conclusion Our real-world study supports the prognostic role of 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 guide clinical decision-making. Further prospective studies are warranted to validate its clinical utility and to optimize dosing strategies that balance efficacy and tolerability.