194P - CD8-to-CD20 lymphocyte ratio is a predictive biomarker for lenvatinib and pembrolizumab efficacy and progression-free survival in advanced endometrial cancer: Updated data

Background

The combination of Pembrolizumab and Lenvatinib shows synergy in treatment of advanced microsatellite stable (MSS) or proficient mismatch repair (pMMR) endometrial cancer, yet only one-third of patients achieve a lasting response. Research into microenvironmental factors seeks to identify markers to select suitable candidates for improved treatment results.

Methods

An open, non-randomized observational association study was conducted across six clinical centers in Siberia and the Far East. The study encompassed an expanded (third iteration of analysis) cohort of 32 patients diagnosed with advanced MSS/pMMR endometrial cancer. Tissue samples were subjected to TSA-associated multiplex immunofluorescence using Vectra 3 (Akoya) to quantify the ratio of CD8-to-CD20 lymphocytes.

Results

In patients who exhibited a positive response to the treatment, there was a notable increase in both the percentage of CD20+ B lymphocytes and the ratio of CD8-to-CD20 lymphocytes when compared to those who did not respond (responders: 0.26% (0.1–1.37%); non-responders: 0.07% (0.00–0.14%), p = 0.0034; responders: 1.45 arb. units (0.58–2.81); non-responders: 20.30 arb. units (3.42–42.08), p = 0.0001). The diagnostic accuracy of the ratio of CD8-to-CD20 lymphocytes was demonstrated by their sensitivity and specificity rates, which were 91.45% for both. Patients with a CD8-to-CD20 lymphocyte ratio of 3.45 or higher had an OR of 10.54 (95% CI: 2.65–37.14, p = 0.0001). Bootstrap validation confirmed minimal bias for the CD8-to-CD20 lymphocyte ratio. Patients with a CD8-to-CD20 lymphocyte ratio less than 3.45 demonstrated improved PFS (CD8-to-CD20 ratio <3.45 vs. ≥3.45: median PFS not reached vs. 6 months, p < 0.0001). However, these factors did not significantly affect overall survival (OS) (CD8-to-CD20 ratio <3.45 vs. ≥3.45: median OS not reached vs. 82 months, p = 0.0736).

Conclusions

The CD8-to-CD20 lymphocyte ratio may act as an effective surrogate marker for immunotargeted therapy in individuals with advanced MSS/pMMR endometrial cancer. The study was supported by the Russian Science Foundation (grant # 20-75-10033-P).

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Tomsk National Research Medical Center.

Funding

The study was supported by the Russian Science Foundation (grant # 20-75-10033-P).

Disclosure

All authors have declared no conflicts of interest.