A potential inflammatory biomarker for advanced endometrial cancer treated with lenvatinib plus pembrolizumab

Abstract

Introduction: To identify prognostic biomarkers that could predict how well patients will respond to lenvatinib/pembrolizumab (LEN/PEM). The utility of certain inflammatory biomarkers in endometrial liquid-based cytology (LBC) or peripheral blood samples, such as neutrophil counts, lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR) were explored.

Methods: The study included 25 patients with advanced or recurrent endometrial cancer who had received LEN/PEM between August 2018 and March 2024. Predictors for overall response (OR), disease control, and progression-free survival, based on neutrophil/lymphocyte counts, NLR scores of the endometrial LBC prior to initial treatment, and peripheral blood prior to initial treatment and prior to LEM/PEM treatment were compared using a receiver operating characteristic curve. Significant predictors were evaluated using the log-rank test, and multivariate analysis.

Results: Although neutrophil counts and NLR score in endometrial LBC prior to initial treatment were better effective predictors for OR, the most accurate predictor of a progression-free status was NLR score in peripheral blood prior to LEM/PEM (0.722, 95% CI: 0.45-0.99, sensitivity: 57.1%, specificity: 94.4%). In peripheral blood prior to LEN/PEM, the lower NLR (NLR <5.39) group had a significantly longer PFS than the higher NLR (5.39 ≤ NLR) group (p = 0.023, median survival: 13.5 vs. 3.0 months), and tended to be independently correlated with PFS (hazard ratio = 2.571; 95% CI = 0.857-7.719; p = 0.092).

Conclusion: Inflammatory biomarkers in endometrial LBC failed to predict the efficacy of LEN/PEM, while peripheral blood NLR score sampled prior to LEN/PEM potentially could be a significant predictor.

Keywords: endometrial cancer; lenvatinib; liquid‐based cytology; lymphocytes; neutrophil‐to‐lymphocyte ratio; pembrolizumab.

FIGURE 1

Flow chart summarizing the retrospective cohort analysis of our study. LEN/PEM, lenvatinib and pembrolizumab; NLR, neutrophil to lymphocyte ratio; LBC, Liquid‐based cytology; ROC, receiver operating characteristic curve.

FIGURE 2

(a) ROC curve of the NLR in peripheral blood prior to LEN/PEM treatment. (b) Scatter diagrams of the neutrophils between endometrial LBC prior to initial treatment and peripheral blood prior to LEN/PEM treatment. (c) Scatter diagrams of the lymphocytes between endometrial LBC prior to initial treatment and peripheral blood prior to LEN/PEM treatment. ROC, receiver operating characteristic; NLR, neutrophil to lymphocyte ratio; LEN/PEM, lenvatinib and pembrolizumab; LBC, Liquid‐based cytology.

FIGURE 3

(a) Progression‐free survival in the lower and higher groups for each item in endometrial LBC prior to initial treatment. (b) Progression‐free survival in the lower and higher groups for each item in peripheral blood prior to LEN/PEM treatment. LBC, Liquid‐based cytology; NLR, neutrophil to lymphocyte ratio; LEN/PEM, lenvatinib and pembrolizumab.

FIGURE 4

Representative LBC photographs of a patient with dMMR, with highly atypical scattered lymphocytes in the background. The patient's neutrophil and lymphocyte counts in endometrial LBC were 50 HPF and 29 HPF (NLR, 1.72), respectively (Left: ×100, Right: ×200).